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.

The static pressure-volume relationship of the respiratory system determined with a computer-controlled ventilator.

The pressure-volume relationship of the respiratory system offers a guideline for setting of ventilators. The occlusion method for determination of the static elastic pressure-volume (Pel(st)/V) relationship is used as a reference and the aim of the study was to improve it with respect to time consumption and precision of recording and analysis. The inspiratory Pel(st)/V curve was determined with a computer-controlled ventilator using its pressure and flow sensors. During an automated procedure, an operator-defined volume history preceded each of a number of study breaths. These were interrupted at different volumes evenly distributed over a predefined volume interval. Total positive end-expiratory pressure (PEEP) was measured and could be separated into its components, external PEEP and auto-PEEP. The volume relationship between the curve and the current tidal volume was defined. An analytical method for definition of a linear segment of the Pel(st)/V curve and determination of its compliance is presented. In eight healthy human anaesthetized subjects duplicate Pel(st)/V curves were studied with respect to compliance and the position along the volume axis of the linear segment. The difference in compliance between measurements was 1.6 +/- 1.3 ml cmH2O(-1) or 1.2 +/- 0.9%. The position of the curve differed between measurements by 15 +/- 10 ml or by 1.1 +/- 0.9%. In a patient with acute lung injury the feasibility of applying a numerical method for a more detailed description of the Pel(st)/V curve was illustrated.

Elastic pressure-volume curves indicate derecruitment after a single deep expiration in anaesthetised and muscle-relaxed healthy man.

BACKGROUND: In acute respiratory distress syndrome, lung volume is lost immediately after positive end-expiratory pressure (PEEP) is removed and is not immediately regained when PEEP is restored to its original value. The aim of this study was to investigate whether the same phenomenon also occurs in cardiopulmonary healthy individuals during anaesthesia and muscle relaxation. METHODS: In 13 anaesthetised and muscle-relaxed patients, inspiratory elastic pressure-volume (Pel-V) curves were, after lung recruitment, obtained from zero end-expiratory airway pressure (ZEEP) and from a PEEP of 5 cmH2O. The curves were aligned on a common volume axis. Differences in lung volumes and compliance (Crs) were calculated at the different airway pressures. RESULTS: At comparable pressures the ZEEP curve showed significantly lower volumes up to an airway pressure of 25 cmH2O. Maximum Crs was similar on the curves obtained from ZEEP and PEEP. However, the lower segments of the curve recorded from PEEP showed lower Crs compared to the curve recorded from ZEEP. CONCLUSION: During anaesthesia and muscle paralysis, the Pel-V relations change immediately when 5 cmH2O of PEEP is removed. This phenomenon is probably mainly caused by closure of small airways and only in a minor part, if any, by formation of atelectasis. This study indicates that under these conditions lung volume might easily be normalised by a large breath producing an airway pressure of 20 cmH2O.

Effects of recruitment of collapsed lung units on the elastic pressure-volume relationship in anaesthetised healthy adults.

BACKGROUND: The elastic pressure-volume (Pel-V) curve of the respiratory system can be used as a guide for improved ventilator management. The understanding of curves recorded for sick patients can be improved with better knowledge of the Pel-V relationship observed in healthy humans. Dynamic Pel-V curves were determined over an extended volume range in 15 anaesthetised and muscle-relaxed healthy humans. The influence of a recruitment manoeuvre was studied. METHODS: Dynamic Pel-V curves were determined during a single prolonged insufflation before and after the recruitment manoeuvre. A mathematical three-segment model of the curve including a linear intermediate segment, delineated by the lower (LIP) and upper (UIP) inflection points, was used for characterisation of the recorded curves. RESULTS: The model gave an adequate description of the recorded Pel-V curves. Before the recruitment manoeuvre, compliance increased until the LIP was reached at 20 cm H2O (1.9 L). Then followed a long linear segment. After the recruitment manoeuvre, compliance increased during insufflation until a LIP was reached at 13 cm H2O (1.2 L). Above the LIP followed a shorter linear segment (compliance = 140 mL/cm H2O) and then an upper segment with decreasing compliance. CONCLUSION: Pel-V curves recorded before and after the recruitment manoeuvre show that large lung compartments close during anaesthesia and that high pressures are needed to achieve recruitment even in the normal lung. Accordingly, the LIP does not define the end of recruitment during insufflation.

Respiratory mechanics in patients ventilated for critical lung disease.

Respiratory mechanics, using flow interruption, was previously studied during the complete breath in healthy ventilated man, numerical techniques relieving constraints regarding flow pattern. The classical linear model of non-Newtonian behaviour was found to be valid. The present study was extended to subjects with critical lung disease. Subjects with acute lung injury (ALI; n = 2), acute respiratory distress syndrome (ARDS; n = 4), and chronic obstructive pulmonary disease (COPD; n = 3) were studied with and without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC) was measured with sulphur hexafluoride (SF6) wash-out. The static pressure-volume (P-V) curve was linear at zero end-expiratory pressure (ZEEP), but nonlinear at PEEP. Its hysteresis was nonsignificant. In ALI/ARDS, PEEP increased lung volume by distension and recruitment, but only by distension in COPD. In ALI/ARDS, resistance was increased, at ZEEP. In COPD, resistance became extremely high during expiration at ZEEP. In ALI/ARDS at ZEEP, non-Newtonian behaviour, representing tissue stress relaxation and pendel-luft, complied with the classical linear model. At PEEP, the non-Newtonian compliance became volume-dependent to an extent correlated to the nonlinearity of the static P-V curve. In COPD, non-Newtonian behaviour was adequately explained only with a model with different inspiratory and expiratory behaviour. The classical model of the respiratory system is valid in ALI/ARDS at ZEEP. More advanced models are needed at PEEP and in COPD.

A single computer-controlled mechanical insufflation allows determination of the pressure-volume relationship of the respiratory system.

OBJECTIVE: To evaluate and further develop a method for determination and mathematical characterisation of the elastic pressure-volume (Pel-V) relationship in mechanically ventilated human subjects during one single modified insufflation with simultaneous determination of resistance of the respiratory system. SUBJECTS: Eight adult non-smoking human subjects without heart, lung, or thoracic cage disease scheduled for non-thoracic surgery. The study was performed in anaesthetised and muscle-relaxed subjects. MEASUREMENTS AND MAIN RESULTS: The Pel-V curve was determined with a computer-controlled Servo Ventilator 900C during a modified insufflation with either constant or sinusoidally varying flow. Pressure and flow were measured with the built-in sensors of the ventilator. Tracheal pressure (Ptr) was calculated by subtracting the pressure drop over the tracheal tube. The elastic recoil pressure in the peripheral lung, Pel, was obtained from the calculated Ptr by subtracting the pressure drop over the airways. Ptr was also directly measured through a catheter. The calculated Ptr gave similar results as the directly measured Ptr, thus indicating the reliability of the signal originating from the ventilator sensor for computation of downstream pressures. The inflection points of the sigmoidal Pel-V curve and the compliance of the linear segment were determined with high reproducibility. CONCLUSIONS: Using one single modified insufflation allows a fast and accurate determination of respiratory mechanics. The Pel-V curves were determined with high reproducibility and were adequately described by a three-segment model of the curve incorporating a linear segment between two asymmetrical non-linear segments.

Pressure-volume curves in acute respiratory failure: automated low flow inflation versus occlusion.

Pressure-volume (P-V) curves of the respiratory system allow determination of compliance and lower and upper inflection points (LIP and UIP, respectively). To minimize lung trauma in mechanical ventilation the tidal volume should be limited to the P-V range between LIP and UIP. An automated low flow inflation (ALFI) technique, using a computer-controlled Servo Ventilator 900C, was compared with a more conventional technique using a series of about 20 different inflated volumes (Pst-V curve). The pressure in the distal lung (Pdist) was calculated by subtraction of resistive pressure drop in connecting tubes and airways. Compliance (Cdist), Pdist(LIP), and Pdist(UIP) were derived from the Pdist-V curve and compared with Cst, Pst(LIP), and Pst(UIP) derived from the Pst-V curve. Nineteen sedated, paralyzed patients (10 with ARDS and 9 with ARF) were studied. We found: Cdist = 2.3 + 0.98 x Cst ml/cm H2O (r = 0.98); Pdist(LIP) = 0.013 + 1.09 x Pst(LIP) cm H2O (r = 0.96). In patients with ARDS: Pdist(UIP) = 4.71 + 0.84 x Pst(UIP) cm H2O (r = 0.94). In ARF, we found differences in UIP between the methods, but discrepancies occurred above tidal volumes and had little practical importance. They may reflect that Pdist comprises dynamic phenomena contributing to pressure in the distal lung at large volumes. Compliance, but not LIP and UIP, could be accurately determined without subtraction of resistive pressure from the pressure measured in the ventilator. We conclude that ALFI, which is fully automated and needing no ventilator disconnection, gives useful clinical information.

Respiratory mechanics in rabbits ventilated with different tidal volumes.

Respiratory mechanics was studied in 11 rabbits at tidal volumes (VT) of 6.7, 10, and 20 ml/kg. Flow interruptions were performed during the full respiratory cycle. The viscoelastic pressure (Pve) was measured as the dynamic elastic pressure (Pel(dyn)) after flow cessation minus the static elastic pressure (Pel(st)). Static elastic and viscoelastic parameters were determined with numerical technique. Static hysteresis was minimal even at large VT. The Pel(st)-V curve was linear at small VT and in 6 animals at moderate VT. In 5 animals at moderate VT and in all animals at large VT, a linear segment with constant compliance was followed by a segment with decreasing compliance. The Pve-V curve could be described with a linear model only at small VT. A non-linear model was needed at increased VT. Compliance increased with VT. Both static and viscoelastic behaviours were linear up to larger volume ranges at large VT compared to moderate VT.

The effects of nitric oxide inhalation on respiratory mechanics and gas exchange during endotoxaemia in the pig.

BACKGROUND: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. METHODS: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO2-, pressure-, and flow signals were recorded. RESULTS: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. CONCLUSION: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.