A new approach in virtopsy: Postmortem ventilation in multislice computed tomography

Although postmortem imaging has gained prominence in the field of forensic medicine, evaluation of the postmortem lung remains problematic. Specifically, differentiation of normal postmortem changes and pathological pulmonary changes is challenging and at times impossible. In this study, five corpses were ventilated using a mechanical ventilator with a pressure of 40 mbar (40.8 cm H(2)O). The ventilation was performed via an endotracheal tube, a larynx mask or a continuous positive airway pressure mask. Postmortem computed tomographic images of the lungs before and with a ventilation of 40 mbar (40.8 cm H(2)O) were evaluated and the lung volumes were measured with segmentation software. Postmortem ventilation led to a clearly visible decrease of both the density in the dependant parts of the lungs and ground glass attenuation, whereas consolidated areas remained unchanged. Furthermore, a mean increase in the lung volume of 2.10 l was seen. Pathological changes such as septal thickening or pulmonary nodules in the lung parenchyma became more detectable with postmortem ventilation. Intracorporal postmortem mechanical ventilation of the lungs appears to be an effective method for enhancing detection of small pathologies of the lung parenchyma as well as for discriminating between consolidation, ground glass attenuation and position-dependent density.

Postmortem ventilation: A new method for improved detection of pulmonary pathologies in forensic imaging

Postmortem imaging has gained prominence in the field of forensic pathology. Even with experience in this procedure, difficulties arise in evaluating pathologies of the postmortem lung. The effect of postmortem ventilation with applied pressures of 10, 20, 30 and 40mbar was evaluated in 10 corpses using simultaneous postmortem computed tomography (pmCT) scans. Ventilation was performed via a continuous positive airway pressure mask (n=5), an endotracheal tube (n=4) and a laryngeal mask (n=1) using a portable home care ventilator. The lung volumes were measured and evaluated by a segmentation technique based on reconstructed CT data. The resulting changes to the lungs were analyzed. Postmortem ventilation at 40mbar induced a significant (p<0.05) unfolding of the lungs, with a mean volume increase of 1.32l. Small pathologies of the lung such as scarring and pulmonary nodules as well as emphysema were revealed, while inner livores were reduced. Even though lower ventilation pressures resulted in a significant (p<0.05) volume increase, pathologies were best evaluated when a pressure of 40mbar was applied, due to the greater reduction of the inner livores. With the ventilation-induced expansion of the lungs, a decrease in the heart diameter and gaseous distension of the stomach was recognized. In conclusion, postmortem ventilation is a feasible method for improving evaluation of the lungs and detection of small lung pathologies. This is because of the volume increase in the air-filled portions of the lung and reduced appearance of inner livores.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases. We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.

Tidal volume single breath washout of two tracer gases--a practical and promising lung function test

Background Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF6) and helium (He) using an ultrasonic flowmeter (USFM). Methods The tracer gas mixture contained 5% SF6 and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart. Results USFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF6 and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%. Conclusion The USFM accurately measured relative changes in SF6 and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF6 and He washout patterns during tidal breathing.

Measurement of ventilation and cardiac related impedance changes with electrical impedance tomography

Introduction Electrical impedance tomography (EIT) has been shown to be able to distinguish both ventilation and perfusion. With adequate filtering the regional distributions of both ventilation and perfusion and their relationships could be analysed. Several methods of separation have been suggested previously, including breath holding, electrocardiograph (ECG) gating and frequency filtering. Many of these methods require interventions inappropriate in a clinical setting. This study therefore aims to extend a previously reported frequency filtering technique to a spontaneously breathing cohort and assess the regional distributions of ventilation and perfusion and their relationship. Methods Ten healthy adults were measured during a breath hold and while spontaneously breathing in supine, prone, left and right lateral positions. EIT data were analysed with and without filtering at the respiratory and heart rate. Profiles of ventilation, perfusion and ventilation/perfusion related impedance change were generated and regions of ventilation and pulmonary perfusion were identified and compared. Results Analysis of the filtration technique demonstrated its ability to separate the ventilation and cardiac related impedance signals without negative impact. It was, therefore, deemed suitable for use in this spontaneously breathing cohort. Regional distributions of ventilation, perfusion and the combined ΔZV/ΔZQ were calculated along the gravity axis and anatomically in each position. Along the gravity axis, gravity dependence was seen only in the lateral positions in ventilation distribution, with the dependent lung being better ventilated regardless of position. This gravity dependence was not seen in perfusion. When looking anatomically, differences were only apparent in the lateral positions. The lateral position ventilation distributions showed a difference in the left lung, with the right lung maintaining a similar distribution in both lateral positions. This is likely caused by more pronounced anatomical changes in the left lung when changing positions. Conclusions The modified filtration technique was demonstrated to be effective in separating the ventilation and perfusion signals in spontaneously breathing subjects. Gravity dependence was seen only in ventilation distribution in the left lung in lateral positions, suggesting gravity based shifts in anatomical structures. Gravity dependence was not seen in any perfusion distributions.

Evolution of gene expression changes in newborn rats after mechanical ventilation with reversible intubation

Mechanical ventilation (MV) is life-saving but potentially harmful for lungs of premature infants. So far, animal models dealt with the acute impact of MV on immature lungs, but less with its delayed effects. We used a newborn rodent model including non-surgical and therefore reversible intubation with moderate ventilation and hypothesized that there might be distinct gene expression patterns after a ventilation-free recovery period compared to acute effects directly after MV. Newborn rat pups were subjected to 8 hr of MV with 60% oxygen (O(2)), 24 hr after injection of lipopolysaccharide (LPS), intended to create a low inflammatory background as often recognized in preterm infants. Animals were separated in controls (CTRL), LPS injection (LPS), or full intervention with LPS and MV with 60% O(2) (LPS + MV + O(2)). Lungs were recovered either directly following (T:0 hr) or 48 hr after MV (T:48 hr). Histologically, signs of ventilator-induced lung injury (VILI) were observed in LPS + MV + O(2) lungs at T:0 hr, while changes appeared similar to those known from patients with chronic lung disease (CLD) with fewer albeit larger gas exchange units, at T:48 hr. At T:0 hr, LPS + MV + O(2) increased gene expression of pro-inflammatory MIP-2. In parallel anti-inflammatory IL-1Ra gene expression was increased in LPS and LPS + MV + O(2) groups. At T:48 hr, pro- and anti-inflammatory genes had returned to their basal expression. MMP-2 gene expression was decreased in LPS and LPS + MV + O(2) groups at T:0 hr, but no longer at T:48 hr. MMP-9 gene expression levels were unchanged directly after MV. However, at T:48 hr, gene and protein expression increased in LPS + MV + O(2) group. In conclusion, this study demonstrates the feasibility of delayed outcome measurements after a ventilation-free period in newborn rats and may help to further understand the time-course of molecular changes following MV. The differences obtained from the two time points could be interpreted as an initial transitory increase of inflammation and a delayed impact of the intervention on structure-related genes.

A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW). Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIII(DTG)), MBNW-derived lung clearance index (LCI), and indices of acinar (S(acin)) and conductive (S(cond)) ventilation inhomogeneity. SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIII(DTG) differed between children with CF and controls, mean±sd was -456.7±492.8 and -88.4±129.1 mg·mol·L(-1), respectively. Abnormal SIII(DTG) was present in 36 (59%) children with CF. SIII(DTG) was associated with LCI (r= -0.58) and S(acin) (r= -0.58), but not with S(cond). In CF, steeply sloping SIII(DTG) potentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.

Influence of end-expiratory level and tidal volume on gravitational ventilation distribution during tidal breathing in healthy adults

Our understanding of regional filling of the lung and regional ventilation distribution is based on studies using stepwise inhalation of radiolabelled tracer gases, magnetic resonance imaging and positron emission tomography. We aimed to investigate whether these differences in ventilation distribution at different end-expiratory levels (EELs) and tidal volumes (V (T)s) held also true during tidal breathing. Electrical impedance tomography (EIT) measurements were performed in ten healthy adults in the right lateral position. Five different EELs with four different V (T)s at each EEL were tested in random order, resulting in 19 combinations. There were no measurements for the combination of the highest EEL/highest V (T). EEL and V (T) were controlled by visual feedback based on airflow. The fraction of ventilation directed to different slices of the lung (VENT(RL1)-VENT(RL8)) and the rate of the regional filling of each slice versus the total lung were analysed. With increasing EEL but normal tidal volume, ventilation was preferentially distributed to the dependent lung and the filling of the right and left lung was more homogeneous. With increasing V (T) and maintained normal EEL (FRC), ventilation was preferentially distributed to the dependent lung and regional filling became more inhomogeneous (p < 0.05). We could demonstrate that regional and temporal ventilation distribution during tidal breathing was highly influenced by EEL and V (T).

Alterations of exhaled nitric oxide in pre-term infants with chronic lung disease

Animal models suggest that reduced nitric oxide (NO) synthase activity results in lower values of exhaled NO (eNO) present at birth in those individuals who are going to develop chronic lung disease of infancy (CLDI). Online tidal eNO was measured in 39 unsedated pre-term infants with CLDI (mean gestational age (GA) 27.3 weeks) in comparison with 23 healthy pre-term (31.6 weeks) and 127 term infants (39.9 weeks) at 44 weeks post-conceptional age, thus after the main inflammatory response. NO output (NO output (V'(NO)) = eNO x flow) was calculated to account for tidal- flow-related changes. Sex, maternal atopic disease and environmental factors (smoking, caffeine) were controlled for. The mean eNO was not different (14.9 ppb in all groups) but V'(NO) was lower in CLDI compared with healthy term infants (0.52 versus 0.63 nL x s(-1)). Values for healthy pre-term infants were between these two groups (0.58 nL x s(-1)). Within all pre-term infants (n = 62), V'(NO) was reduced in infants with low GA, high clinical risk index for babies scores and longer duration of oxygen therapy but not associated with post-natal factors, such as ventilation or corticosteroid treatment. After accounting for flow, the lower nitric oxide output in premature infants with chronic lung disease of infancy is consistent with the hypothesis of nitric oxide metabolism being involved in chronic lung disease of infancy.

Risk factors for reperfusion injury after lung transplantation

OBJECTIVE: To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. DESIGN AND SETTING: Retrospective study in the surgical intensive care unit (ICU) of a university hospital. METHODS: We collected data on 60 lung transplantation donor/recipient pairs from June 1993 to May 2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. RESULTS: The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48[Symbol: see text]h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p[Symbol: see text]=[Symbol: see text]0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48[Symbol: see text]h after surgery (p[Symbol: see text]=[Symbol: see text]0.014). The extubation was delayed (p[Symbol: see text]=[Symbol: see text]0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p[Symbol: see text]<[Symbol: see text]0.01). CONCLUSIONS: Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigated.

Quantification of atelectatic lung volumes in two different porcine models of ARDS

BACKGROUND: Cyclic recruitment during mechanical ventilation contributes to ventilator associated lung injury. Two different pathomechanisms in acute respiratory distress syndrome (ARDS) are currently discussed: alveolar collapse vs persistent flooding of small airways and alveoli. We compare two different ARDS animal models by computed tomography (CT) to describe different recruitment and derecruitment mechanisms at different airway pressures: (i) lavage-ARDS, favouring alveolar collapse by surfactant depletion; and (ii) oleic acid ARDS, favouring alveolar flooding by capillary leakage. METHODS: In 12 pigs [25 (1) kg], ARDS was randomly induced, either by saline lung lavage or oleic acid (OA) injection, and 3 animals served as controls. A respiratory breathhold manoeuvre without spontaneous breathing at different continuous positive airway pressure (CPAP) was applied in random order (CPAP levels of 5, 10, 15, 30, 35 and 50 cm H(2)O) and spiral-CT scans of the total lung were acquired at each CPAP level (slice thickness=1 mm). In each spiral-CT the volume of total lung parenchyma, tissue, gas, non-aerated, well-aerated, poorly aerated, and over-aerated lung was calculated. RESULTS: In both ARDS models non-aerated lung volume decreased significantly from CPAP 5 to CPAP 50 [oleic acid lung injury (OAI): 346.9 (80.1) to 96.4 (48.8) ml, P<0.001; lavage-ARDS: 245 17.6) to 42.7 (4.8) ml, P<0.001]. In lavage-ARDS poorly aerated lung volume decreased at higher CPAP levels [232 (45.2) at CPAP 10 to 84 (19.4) ml at CPAP 50, P<0.001] whereas in OAI poorly aerated lung volume did not vary at different airway pressures. CONCLUSIONS: In both ARDS models well-aerated and non-aerated lung volume respond to different CPAP levels in a comparable fashion: Thus, a cyclical alveolar collapse seems to be part of the derecruitment process also in the OA-ARDS. In OA-ARDS, the increase in poorly aerated lung volume reflects the specific initial lesion, that is capillary leakage with interstitial and alveolar oedema.

Alternative protocol to initiate high-frequency oscillatory ventilation: an experimental study

INTRODUCTION: The objective was to study the effects of a novel lung volume optimization procedure (LVOP) using high-frequency oscillatory ventilation (HFOV) upon gas exchange, the transpulmonary pressure (TPP), and hemodynamics in a porcine model of surfactant depletion. METHODS: With institutional review board approval, the hemodynamics, blood gas analysis, TPP, and pulmonary shunt fraction were obtained in six anesthetized pigs before and after saline lung lavage. Measurements were acquired during pressure-controlled ventilation (PCV) prior to and after lung damage, and during a LVOP with HFOV. The LVOP comprised a recruitment maneuver with a continuous distending pressure (CDP) of 45 mbar for 2.5 minutes, and a stepwise decrease of the CDP (5 mbar every 5 minute) from 45 to 20 mbar. The TPP level was identified during the decrease in CDP, which assured a change of the PaO2/FIO2 ratio < 25% compared with maximum lung recruitment at CDP of 45 mbar (CDP45). Data are presented as the median (25th-75th percentile); differences between measurements are determined by Friedman repeated-measures analysis on ranks and multiple comparisons (Tukey's test). The level of significance was set at P < 0.05. RESULTS: The PaO2/FiO2 ratio increased from 99.1 (56.2-128) Torr at PCV post-lavage to 621 (619.4-660.3) Torr at CDP45 (CDP45) (P < 0.031). The pulmonary shunt fraction decreased from 51.8% (49-55%) at PCV post-lavage to 1.03% (0.4-3%) at CDP45 (P < 0.05). The cardiac output and stroke volume decreased at CDP45 (P < 0.05) compared with PCV, whereas the heart rate, mean arterial pressure, and intrathoracic blood volume remained unchanged. A TPP of 25.5 (17-32) mbar was required to preserve a difference in PaO2/FIO2 ratio < 25% related to CDP45; this TPP was achieved at a CDP of 35 (25-40) mbar. CONCLUSION: This HFOV protocol is easy to perform, and allows a fast determination of an adequate TPP level that preserves oxygenation. Systemic hemodynamics, as a measure of safety, showed no relevant deterioration throughout the procedure.

Initiation of high-frequency oscillatory ventilation and its effects upon cerebral circulation in pigs: an experimental study

BACKGROUND: Current practice at high-frequency oscillatory ventilation (HFOV) initiation is a stepwise increase of the constant applied airway pressure to achieve lung recruitment. We hypothesized that HFOV would lead to more adverse cerebral haemodynamics than does pressure controlled ventilation (PCV) in the presence of experimental intracranial hypertension (IH) and acute lung injury (ALI) in pigs with similar mean airway pressure settings. METHODS: In 12 anesthetized pigs (24-27 kg) with IH and ALI, mean airway pressure (P(mean)) was increased (to 20, 25, 30 cm H(2)O every 30 min), either with HFOV or with PCV. The order of the two ventilatory modes (cross-over) was randomized. Mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) (fluorescent microspheres), cerebral metabolism, transpulmonary pressures (P(T)), and blood gases were determined at each P(mean) setting. Our end-points of interest related to the cerebral circulation were ICP, CPP and CBF. RESULTS: CBF and cerebral metabolism were unaffected but there were no differences between the values for HFOV and PCV. ICP increased slightly (HFOV median +1 mm Hg, P<0.05; PCV median +2 mm Hg, P<0.05). At P(mean) setting of 30 cm H(2)O, CPP decreased during HFOV (median -13 mm Hg, P<0.05) and PCV (median -17 mm Hg, P<0.05) paralleled by a decrease of MAP (HFOV median -11 mm Hg, P<0.05; PCV median -13 mm Hg, P<0.05). P(T) increased (HFOV median +8 cm H(2)O, P<0.05; PCV median +8 cm H(2)O, P<0.05). Oxygenation improved and normocapnia maintained by HFOV and PCV. There were no differences between both ventilatory modes. CONCLUSIONS: In animals with elevated ICP and ALI, both ventilatory modes had effects upon cerebral haemodynamics. The effects upon cerebral haemodynamics were dependent of the P(T) level without differences between both ventilatory modes at similar P(mean) settings. HFOV seems to be a possible alternative ventilatory strategy when MAP deterioration can be avoided.

Lung aeration during sleep

BACKGROUND: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

Non-invasive neurally adjusted ventilatory assist in rabbits with acute lung injury

OBJECTIVE: Neurally adjusted ventilatory assist uses the electrical activity of the diaphragm (EAdi)-a pneumatically-independent signal-to control the timing and pressure of the ventilation delivered, and should not be affected by leaks. The aim of this study was to evaluate whether NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface. DESIGN AND SETTING: Prospective, controlled experimental study in an animal laboratory. ANIMALS: Ten rabbits, anesthetized, mechanically ventilated. INTERVENTIONS: Following lung injury, the following was performed in sequential order: (1) NAVA delivered via oral endotracheal tube with PEEP; (2) same as (1) without PEEP; (3) non-invasive NAVA at unchanged NAVA level and no PEEP via a single nasal prong; (4) no assist; (5) non-invasive NAVA at progressively increasing NAVA levels. MEASUREMENTS AND RESULTS: EAdi, esophageal pressure, blood gases and hemodynamics were measured during each condition. For the same NAVA level, the mean delivered pressure above PEEP increased from 3.9[Symbol: see text]+/-[Symbol: see text]1.4[Symbol: see text]cmH(2)O (intubated) to 7.5[Symbol: see text]+/-[Symbol: see text]3.8[Symbol: see text]cmH(2)O (non-invasive) (p[Symbol: see text]<[Symbol: see text]0.05) because of increased EAdi. No changes were observed in PaO(2) and PaCO(2). Increasing the NAVA level fourfold during non-invasive NAVA restored EAdi and esophageal pressure swings to pre-extubation levels. Triggering (106[Symbol: see text]+/-[Symbol: see text]20[Symbol: see text]ms) and cycling-off delays (40[Symbol: see text]+/-[Symbol: see text]21[Symbol: see text]ms) during intubation were minimal and not worsened by the leak (95[Symbol: see text]+/-[Symbol: see text]13[Symbol: see text]ms and 33[Symbol: see text]+/-[Symbol: see text]9[Symbol: see text]ms, respectively). CONCLUSION: NAVA can be effective in delivering non-invasive ventilation even when the interface with the patient is excessively leaky, and can unload the respiratory muscles while maintaining synchrony with the subject's demand.