Diederik Gommers

Lung overinflation without positive end-expiratory pressure promotes bacteremia after experimental Klebsiella pneumoniae inoculation

AbstractObjective: To determine the effect of peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) on the development of bacteremia with Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated rats. Design: Prospective, randomized, animal study. Setting: Experimental intensive care unit of a University. Subjects: Eighty male Sprague Daw-ley rats. Interventions: Intratracheal inoculation with 100 µl of saline containing 3.5−5.0×105 colony forming units (CFUs) K. pneumoniae/ml. Pressure-controlled ventilation (frequency 30 bpm; I/E ratio=1:2; FIO2=1.0) for 180 min at the following settings (PIP/PEEP in cmH2O): 13/3 (n=16); 13/0 (n=16); 30/10 (n=16) and 30/0 (n=16), starting 22 h after inoculation. Arterial blood samples were obtained and cultured before and 180 min after mechanical ventilation and immediately before sacrifice in two groups of non-ventilated control animals (n=8 per group). After sacrifice, the lungs were homogenized to determine the number of CFUs K. pneumoniae. Measurements and results: The number of CFUs recovered from the lungs was comparable in all experimental groups. After 180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/0, whereas only 2,0 and 2 animals were positive in 13/3,13/0 and 30/10, respectively (p<0.05 group 30/0 versus all other groups). Conclusions: These data show that 3 h of mechanical ventilation with a PIP of 30 cmH2O without PEEP in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH2O PEEP at such PIP reduces ventilation-induced K. pneumoniae bacteremia.

In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function

ObjectiveThe adult respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (RDS) are characterized by high permeability pulmonary edema which contains plasma-derived proteins inhibiting pulmonary surfactant function. Currently, discussion continues as to what dose of surfactant is required for treatment of these syndromes.DesignThe purpose of this study was to investigate the amount of exogenous surfactant needed to overcome the inhibitory components in human plasma. Male adult rats suffering from respiratory failure due to surfactant depletion after whole-lung lavage received human plasma (4 ml/kg body weight) mixed with surfactant at different concentrations, intratracheally. Rats receiving surfactant only at different concentrations served as controls. Blood gas analysis was performed.Measurements and resultsIt was demonstrated that plasma (4 ml/kg≈273 mg, plasma proteins/kg) mixed with surfactant at 300 mg/kg was able to increase and maintain PaO2 at normal values. Plasma mixed with surfactant at 100 mg/kg, after initial restoration of blood gases, showed deterioration of PaO2 values. Plasma mixed with surfactant at a dose of 50 mg/kg did not improve PaO2 whereas surfactant at 50 mg/kg, without plasma, restored blood gases to pre-lavage values.ConclusionIt is concluded that approximately 1 mg surfactant phospholipids is required to overcome the inhibitory effect of approximately 1 mg plasma proteins. For clinical practice this means that an excess of surfactant should be given, or repeatedly be substituted (“titrated”) at low concentrations, until blood gases improve.

Multicenter randomized comparison of xenon and isoflurane on left ventricular function in patients undergoing elective surgery

Background: Volatile anesthetics are commonly used for general anesthesia. However, these can induce profound cardiovascular alterations. Xenon is a noble gas with potent anesthetic and analgesic properties. However, it is uncertain whether xenon alters myocardial function. The aim of this study was therefore to investigate left ventricular function during anesthesia with xenon compared with isoflurane. Methods: The authors performed a randomized multicenter trial to compare xenon with isoflurane with respect to cardiovascular stability and adverse effects in patients without cardiac diseases scheduled for elective surgery. Two hundred fifty-nine patients were enrolled in this trial, of which 252 completed the study according to the protocol. Patients were anesthetized with xenon or isoflurane, respectively. Before administration of the study drugs and at four time points, the effects of both anesthetics on left ventricular function were investigated using transesophageal echocardiography. Results: Global hemodynamic parameters were significantly altered using isoflurane (P < 0.05 vs. baseline), whereas xenon only decreased heart rate (P < 0.05 vs. baseline). In contrast to xenon, left ventricular end-systolic wall stress decreased significantly in the isoflurane group (P < 0.05 vs. baseline). Velocity of circumferential fiber shortening was decreased significantly in the xenon group but showed a more pronounced reduction during isoflurane administration (P < 0.05 vs. baseline). The contractile index (difference between expected and actually measured velocity of circumferential fiber shortening) as an independent parameter for left ventricular function was significantly decreased after isoflurane (P < 0.0001) but unchanged using xenon. Conclusions: Xenon did not reduce contractility, whereas isoflurane decreased the contractile index, indicating that xenon enables favorable cardiovascular stability in patients without cardiac diseases.

Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone.

ObjectiveTo study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DesignProspective randomized, controlled study. SettingLaboratory and animal facility of a large university. SubjectsTwelve adult New Zealand white rabbits. InterventionsRespiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/ kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. Measurements and Main ResultsBefore and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by-breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 ± 7 torr [8.2 ± 0.9 kPa] to 470 ± 47 torr [62.6 ± 6.2 kPa]) and in functional residual capacity (7.6 ± 1.4 to 17.7 ± 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. ConclusionsThe findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance. (Crit Care Med 1993; 21:567–574)

The open lung concept: pressure-controlled ventilation is as effective as high-frequency oscillatory ventilation in improving gas exchange and lung mechanics in surfactant-deficient animals.

Objective: To demonstrate in experimental animals with respiratory insufficiency that under well-defined conditions, commercially available ventilators allow settings which are as effective as high frequency oscillatory ventilators (HFOV), with respect to the levels of gas exchange, protein infiltration, and lung stability. Design: Prospective, randomized, animal study. Setting: Experimental laboratory of a university. Subjects: 18 adult male Sprague-Dawley rats. Interventions: Lung injury was induced by repeated whole-lung lavage. Thereafter, the animals were assigned to pressure-controlled ventilation (PCV) plus The Open Lung Concept (OLC) or HFOV plus OLC (HFOOLC). In both groups, an opening maneuver was performed by increasing airway pressures to improve the arterial oxygen tension/fractional inspired oxygen (PaO2/FIO2) ratio to L 500 mm Hg; thereafter, airway pressures were reduced to minimal values, which kept PaO2/FIO2 L 500 mm Hg. Pressure amplitude was adjusted to keep CO2 as close as possible in the normal range. Measurements and results: Airway pressure, blood gas tension, and arterial blood pressure were recorded every 30 min. At the end of the 3-h study period, a pressure-volume curve was recorded and bronchoalveolar lavage was performed to determine protein content. After the recruitment maneuver, the resulting mean airway pressure to keep a PaO2/FIO2 L 500 mm Hg was 25 ± 1.3 cm H2O during PCVOLC and 25 ± 0.5 cm H2O during HFOVOLC. Arterial oxygenation in both groups was above L 500 mm Hg and arterial carbon dioxide tension was kept close to the normal range. No differences in mean arterial pressure, lung mechanics and protein influx were found between the two groups. Conclusions: This study shows that in surfactant-deficient animals, PCV, in combination with a recruitment maneuver, opens atelectatic lung areas and keeps them open as effectively as HFOV.

Chest electrical impedance tomography examination, data analysis, terminology, clinical use and recommendations: consensus statement of the TRanslational EIT developmeNt stuDy group

Electrical impedance tomography (EIT) has undergone 30 years of development. Functional chest examinations with this technology are considered clinically relevant, especially for monitoring regional lung ventilation in mechanically ventilated patients and for regional pulmonary function testing in patients with chronic lung diseases. As EIT becomes an established medical technology, it requires consensus examination, nomenclature, data analysis and interpretation schemes. Such consensus is needed to compare, understand and reproduce study findings from and among different research groups, to enable large clinical trials and, ultimately, routine clinical use. Recommendations of how EIT findings can be applied to generate diagnoses and impact clinical decision-making and therapy planning are required. This consensus paper was prepared by an international working group, collaborating on the clinical promotion of EIT called TRanslational EIT developmeNt stuDy group. It addresses the stated needs by providing (1) a new classification of core processes involved in chest EIT examinations and data analysis, (2) focus on clinical applications with structured reviews and outlooks (separately for adult and neonatal/paediatric patients), (3) a structured framework to categorise and understand the relationships among analysis approaches and their clinical roles, (4) consensus, unified terminology with clinical user-friendly definitions and explanations, (5) a review of all major work in thoracic EIT and (6) recommendations for future development (193 pages of online supplements systematically linked with the chief sections of the main document). We expect this information to be useful for clinicians and researchers working with EIT, as well as for industry producers of this technology.

INTRATRACHEAL SURFACTANT ADMINISTRATION RESTORES GAS EXCHANGE IN EXPERIMENTAL ADULT RESPIRATORY DISTRESS SYNDROME ASSOCIATED WITH VIRAL PNEUMONIA

The effect of intratracheal surfactant administration was studied in rats with adult respiratory distress syndrome associated with infection with nebulized Sendai virus. Thirty-six hours after infection, animals (n = 7) showed severely impaired gas exchange and acidosis during artificial ventilation (Pao2 = 152.2 ± 18.7, Paco2 = 65.3 ± 29.2, pH = 7.26 ± 0.11) with a pressure-controlled mode, standard frequency of 35/min, peak airway pressure of 15 cm H2O (15/0), inspiratory/expiratory ratio of 1:2, and F102 = 1. Gas exchange improved (P =0.02) with increased ventilator pressures with PEEP (25/4). Forty-eight hours after infection, blood gas tensions could no longer be significantly improved by these same ventilator settings (Pao2 = 123.8 ± 31.0, Paco2 =95.2 ± 43.6, pH7.22 ± 0.26, n = 9). At this time, surfactant replacement dramatically increased arterial oxygenation within 5 min (Pao2 = 389.4 ± 79.9) and resulted in a fourfold increase in Pao2 within 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of respiratory failure during adult respiratory distress syndrome associated with viral pneumonia.

End-expiratory lung volume during mechanical ventilation: A comparison with reference values and the effect of positive end-expiratory pressure in intensive care unit patients with different lung conditions

IntroductionFunctional residual capacity (FRC) reference values are obtained from spontaneous breathing patients, and are measured in the sitting or standing position. During mechanical ventilation FRC is determined by the level of positive end-expiratory pressure (PEEP), and it is therefore better to speak of end-expiratory lung volume. Application of higher levels of PEEP leads to increased end-expiratory lung volume as a result of recruitment or further distention of already ventilated alveoli. The aim of this study was to measure end-expiratory lung volume in mechanically ventilated intensive care unit (ICU) patients with different types of lung pathology at different PEEP levels, and to compare them with predicted sitting FRC values, arterial oxygenation, and compliance values.MethodsEnd-expiratory lung volume measurements were performed at PEEP levels reduced sequentially (15, 10 and then 5 cmH2O) in 45 mechanically ventilated patients divided into three groups according to pulmonary condition: normal lungs (group N), primary lung disorder (group P), and secondary lung disorder (group S).ResultsIn all three groups, end-expiratory lung volume decreased significantly (P < 0.001) while PEEP decreased from 15 to 5 cmH2O, whereas the ratio of arterial oxygen tension to inspired oxygen fraction did not change. At 5 cmH2O PEEP, end-expiratory lung volume was 31, 20, and 17 ml/kg predicted body weight in groups N, P, and S, respectively. These measured values were only 66%, 42%, and 34% of the predicted sitting FRC. A correlation between change in end-expiratory lung volume and change in dynamic compliance was found in group S (P < 0.001; R2 = 0.52), but not in the other groups.ConclusionsEnd-expiratory lung volume measured at 5 cmH2O PEEP was markedly lower than predicted sitting FRC values in all groups. Only in patients with secondary lung disorders were PEEP-induced changes in end-expiratory lung volume the result of derecruitment. In combination with compliance, end-expiratory lung volume can provide additional information to optimize the ventilator settings.

Impact of intraoperative donor management on short-term renal function after laparoscopic donor nephrectomy

ObjectiveTo determine whether intraoperative diuresis, postoperative recovery, and early graft function differ between laparoscopic open nephrectomy (LDN) and open donor nephrectomy (ODN). Summary Background DataLaparoscopic donor nephrectomy can reduce donor complications in terms of decreased pain and shorter convalescence. Although its technical feasibility has been established, concerns have been raised about the impaired renal function resulting from pneumoperitoneum and short- and long-term function of kidneys removed by LDN. MethodsBetween December 1997 and December 2000, 89 LDNs were performed at the authors’ institution. These were compared with 83 conventional ODNs performed between January 1994 and December 1997. Graft function, intraoperative variables, and clinical outcome were compared. ResultsLaparoscopic donor nephrectomy was attempted in 89 patients and completed in 91% (81/89). Length of hospital stay was significantly shorter in the laparoscopic group. During kidney dissection, the amount of fluids administered and intraoperative diuresis were significantly lower for LDN. In recipients, mean serum creatinine was higher after LDN compared with ODN 1 day after surgery. From postoperative days 2 until 28, there were no differences in serum creatinine. Graft survival rates were similar for LDN and ODN. ConclusionsDonors can benefit from an improvement in postoperative recovery after LDN. Assessment of an adequate perioperative hydration protocol is mandatory to ensure optimal kidney quality during laparoscopic procurement. The initial graft survival and function rates justify continued development and adoption of LDN.

Electrical impedance tomography measured at two thoracic levels can visualize the ventilation distribution changes at the bedside during a decremental positive end-expiratory lung pressure trial

IntroductionComputed tomography of the lung has shown that ventilation shifts from dependent to nondependent lung regions. In this study, we investigated whether, at the bedside, electrical impedance tomography (EIT) at the cranial and caudal thoracic levels can be used to visualize changes in ventilation distribution during a decremental positive end-expiratory pressure (PEEP) trial and the relation of these changes to global compliance in mechanically ventilated patients.MethodsVentilation distribution was calculated on the basis of EIT results from 12 mechanically ventilated patients after cardiac surgery at a cardiothoracic ICU. Measurements were taken at four PEEP levels (15, 10, 5 and 0 cm H2O) at both the cranial and caudal lung levels, which were divided into four ventral-to-dorsal regions. Regional compliance was calculated using impedance and driving pressure data.ResultsWe found that tidal impedance variation divided by tidal volume significantly decreased on caudal EIT slices, whereas this measurement increased on the cranial EIT slices. The dorsal-to-ventral impedance distribution, expressed according to the center of gravity index, decreased during the decremental PEEP trial at both EIT levels. Optimal regional compliance differed at different PEEP levels: 10 and 5 cm H2O at the cranial level and 15 and 10 cm H2O at the caudal level for the dependent and nondependent lung regions, respectively.ConclusionsAt the bedside, EIT measured at two thoracic levels showed different behavior between the caudal and cranial lung levels during a decremental PEEP trial. These results indicate that there is probably no single optimal PEEP level for all lung regions.