Developmental dysplasia of the hip in children with Down syndrome: comparison of clinical and radiological examinations in a local cohort.

Guidelines for children with Down syndrome (DS) suggest to perform an annual hip screening to enable early detection of developmental dysplasia of the hip (DDH). How to perform this screening is not described. Delayed detection can result in disabling osteoarthritis of the hip. Therefore, we determined the association between clinical history, physical, and radiological examination in diagnosing DDH in children with DS. Referral centers for children with DS were interviewed to explore variety of hip examination throughout the Netherlands. Clinical features of 96 outclinic children were retrospectively collected. Clinical history was taken, physical examination was performed, and X-ray of the hip was analyzed. All the referral centers performed physical examination and clinical history; however, 20% performed X-ray. Following physical examination according to Galeazzi test 26.9% and to limited abduction 10.8% of the outclinic-studied children were at risk for DDH. Radiological examination showed moderate or severe abnormal deviating migration rate of 14.6% resp. 11.5% in the right and left hip. However, no association between clinical history, physical examination, and radiological examination was found.Conclusion: Clinical history and physical examination are insufficient to timely detect DDH in children with Down syndrome. Thereby regular radiological examination of the hip is advised. What is Known: • Developmental dysplasia of the hip (DDH) in people with Down syndrome (DS) develops during childhood. • Guidelines for medical support of children with DS suggest an annual hip screening to enable early detection of hip damaging. How to perform this annual screening is not described. What is New: • This study shows no association between clinical history, physical and radiological examination of the hip. • We recommend regular radiological examination of the hip in children with DS in order to identify DDH early up to 16 years of age.

Prevalence of systemic air-embolism after prolonged cardiopulmonary resuscitation in newborns: A pilot study.

BACKGROUND: Chest compressions (CC) during cardiopulmonary resuscitation (CPR) are the cornerstone of adult CPR protocols and are meant to restore circulation and improve outcome. Although adverse effects such as air-embolisms have been reported, these are rare and considered to be outweighed by beneficial effect. In newborns, however, the lung tissue is more fragile. Thus, the high intra-thoracic pressures resulting from CC may make the newborns more vulnerable for air-embolisms. OBJECTIVES: We studied the postmortem prevalence of air-embolism in neonates that have received CPR. METHODS: Prospective cohort analysis of newborns receiving CC during CPR. CPR was performed by trained staff according to ILCOR guidelines, in a tertiary hospital. Air-embolisms were sought after using CT/MRI and autopsy. RESULTS: During a 61/2 year period (2007-2014), n = 56 newborns received CC. Newborns were resuscitated following severe perinatal hypoxia, or due to complications during NICU treatment. In n = 14 (25.0%) circulation could not be restored (mean CPR duration: 32.7 ± 15.2 min). Post-mortem CT/MRI was performed in n = 9, of whom n = 8 (88.9%) had air-embolisms. Autopsy was performed in n = 9. The air-embolisms could not be retraced on autopsy except for n = 1 patient. In patients with CPR resulting in restored circulation (n = 42), no CT or MRI was performed for comparison due to radiation and/or hemodynamic instability. Cerebral ultrasound could not identify or exclude air-embolisms in this subgroup. CONCLUSIONS: Post-mortem CT after prolonged resuscitation showed a high prevalence of intravascular air-embolism. Autopsy was not suited to detect air-embolism. The clinical importance of air-embolisms on the lethal outcome needs further research.

Development of children with symptomatic intracranial hemorrhage born after vacuum extraction.

Vacuum extraction significantly reduces perinatal morbidity/mortality. Increased occurrence of intracranial hemorrhage has been associated with vacuum extraction and is multifactorial; a causative effect is not assumed. Long-term developmental outcome data in this specific subpopulation are lacking and may differ from non-vacuum extraction-associated intracranial hemorrhage. Long-term follow-up of children with symptomatic vacuum extraction-associated intracranial hemorrhage was retrospectively analyzed using Bayley Scales of Infant Development. Twenty-five newborns were identified with symptomatic intracranial hemorrhage after vacuum extraction. Motor development was severely impaired in 4 children (16%, Bayley Scale score <55), moderately impaired in 5 children (20%, Bayley Scale score 55-69) and mildly impaired in 2 children (8%, Bayley Scale score 70-84). Mental development was severely impaired in 2 children (8%), moderately impaired in 3 children (12%) and mildly impaired in 5 children (20%). Impaired outcome was associated with parenchymal injury and seems to be a higher reported outcome in non-vacuum extraction-associated intracranial hemorrhage. The high prevalence of impaired development in symptomatic vacuum extraction-associated intracranial hemorrhage necessitates long-term follow-up.

Long-term outcome in pyridoxine-dependent epilepsy.

AIM: The long-term outcome of the Dutch pyridoxine-dependent epilepsy cohort and correlations between patient characteristics and follow-up data were retrospectively studied. METHOD: Fourteen patients recruited from a national reference laboratory were included (four males, 10 females, from 11 families; median age at assessment 6y; range 2y 6mo-16y). The following data were retrieved: sex; age at seizure onset; age at the start of pyridoxine therapy; level of urinary alpha-aminoadipic semialdehyde; antiquitin mutations; developmental milestones; evaluation of neurocognitive functioning and school career; magnetic resonance imaging (MRI) and electroencephalography (EEG) assessments. RESULTS: Pyridoxine was started antenatally in two children, in the first week of life in five, in the first month of life in three, or after the first month of life (range 2.5-8mo) in four. No child was physically disabled; however, only five walked at 2 years of age. Mental development was delayed in most: median IQ or developmental index was 72 (SD 19). Pyridoxine monotherapy controlled seizures in 10 of 14 children, whereas four needed additional antiepileptic drugs. Seizure persistence, antiepileptic drugs (other than pyridoxine), EEG background, and epileptiform activity were not associated with outcome. On neonatal MRI, structural and white matter abnormalities occurred in five of eight children; on follow-up, the number of abnormal MRIs was increased. Delayed initiation of pyridoxine medication and corpus callosum abnormalities were significantly associated with unfavourable neurodevelopmental outcome, but normal follow-up imaging did not predict a good outcome. INTERPRETATION: Outcome of patients with pyridoxine-dependent epilepsy remains poor. Individual outcome cannot be predicted by the evaluated characteristics. We suggest that collaborated research in structured settings could help to improve treatment strategies and outcome for pyridoxine-dependent epilepsy.

Artefacts in the amplitude-integrated EEG background pattern of a full-term asphyxiated neonate caused by diaphragm spasms.

The amplitude-integrated EEG (aEEG) is used to detect neonatal seizures in neonates with asphyxia, and despite limited data-information compared with standard EEG, aEEG is increasingly used as routine monitoring in neonatal intensive care units due to the logistic advantages. In addition, the aEEG background is of prognostic value in these infants. However, aEEG artefacts can lead to an erroneous interpretation of the background pattern. We report a full-term infant with severe perinatal asphyxia with diaphragm spasms that caused a significant alteration in aEEG background pattern. After administration of a neuromuscular blocker, the aEEG background transformed from discontinuous low-voltage pattern to a flat trace. The aEEG background pattern can be misinterpreted by electrical activity of non-cerebral origin. Administration of neuromuscular blockers is a rapid method to differentiate between cerebral and muscular activity on the aEEG when EEG is not (yet) available.

[Procedural sedation with propofol in non-painful interventions in children]. / Sedatie met propofol voor niet-pijnlijke procedures bij kinderen.

UNLABELLED: Propofol is the sedative of choice in our hospital for all procedural sedations in children older than 3 months. Data were collected from all patients who underwent PSA with propofol in the period from November 2007 to December 2009. The procedure was performed by a paediatrician experienced in airway management, sedation and paediatric IC, and a specialized nurse. Patient characteristics, American Society of Anesthesiologists (ASA) classification, vital parameters and propofol dosage were registered on specially designed forms. Patient data were analyzed and compared with data from a non-matched historical cohort of patients who in the past had undergone PSA with chloral hydrate. RESULTS: 204 procedural sedations with intravenous propofol were performed in 196 patients. The mean cumulative induction dose was 3.39 mg/kg (SD: 1.34) and the mean maintenance dose was 4.05 mg/kg/h (SD: 2.23). The success rate was 99.5%, compared to 88.6% in the cohort that had received PSA with chloral hydrate. 1 procedure was aborted because of desaturation due to an obstructed airway, for which a jaw thrust was performed. No complications were observed in 199 procedures (97.5%). In 4 procedures a mild and transient desaturation (85-89%) occurred. CONCLUSION: The results suggest that propofol can be used safely and is effective for procedural sedation in selected children, provided that PSA is performed by experienced and trained staff.

A child with a abnormal neck posture after doing a head-over-heels.

Torticollis in children is a frequently encountered problem. Whereas non-traumatic torticollis usually allows a non-urgent work-up, traumatic torticollis-even in the absence of neurologic abnormalities-needs prompt analysis for structural damage of the spinal column and myelum. Even a trauma as mild as a head-over-heels may result in atlanto-axial subluxation as demonstrated by this patient as described in this case report. In all children with post-traumatic torticollis, further analysis is needed. Atlanto-axial subluxation without neurological or radiological abnormalities can be treated conservatively with a soft collar and analgesics.

Is it useful to measure C-reactive protein and leukocytes in patients with prelabor rupture of membranes?

Neonatal infection is the main complication of prelabor rupture of membranes (PROM). We studied the accuracy of measuring C-reactive protein (CRP) and leukocytes in maternal serum to predict neonatal infection. We performed a retrospective cohort study in two hospitals in the Netherlands between 2003 and 2006. We included consecutive women hospitalized for PROM. In both hospitals, CRP and leukocytes were measured routinely in maternal serum every 2 days until delivery. End points considered were clinical neonatal infection and proven neonatal sepsis. The accuracy of CRP and leukocytes was assessed using receiver operating characteristic (ROC) analysis. We included 299 women with PROM, 12 of whom had a twin pregnancy. Gestational age at inclusion varied between 26 weeks and 0 days and 41 weeks and 5 days with a median of 37 weeks and 3 days. In 47 women (16%), the neonate developed a clinical infection. The areas under the ROC curve of CRP and leukocytes in the prediction of clinical neonatal infection were 0.61 and 0.62, respectively. Of the 47 infected neonates, six neonates (2%) had a proven neonatal sepsis. In the mothers of these septic neonates, maternal CRP did not rise above 50 mg/L and leukocyte values varied between 9.8 and 25.8 x 10 (9)/L. In women with PROM, CRP and leukocytes should not be measured routinely.

Risk factors for the deterioration of oxygenation ratio in ventilated intensive care unit patients: a retrospective cohort study.

PURPOSE: The aim of the study is to determine which factors are associated with the deterioration of Pao(2)/fraction of inspired oxygen (Fio(2)) ratio in patients with normal oxygenation at admission and ventilated according to a lung protective ventilation strategy. MATERIALS AND METHODS: Retrospective cohort study of ventilated (>/=3 days) intensive care unit patients with an admission Pao(2)/Fio(2) ratio of 300 mm Hg or higher (n = 105). Patients who developed lung injury (Pao(2)/Fio(2) ratio, <300 mm Hg) on day 7 (n = 37) were compared to those who did not (n = 68), with regard to ventilator settings, gas exchange variables, and lung injury risk factors. RESULTS: Mean +/- SD of administered tidal volume was 7.9 +/- 1.3 mL/kg. Patients who developed lung injury were older (P = .019), had lower Pao(2) (P = .009), higher Paco(2) (P = .045), and lower Pao(2)/Fio(2) ratio (P = .002) at admission. Postoperative state (Hazard risk [HR], 5.1) and controlled ventilation mode (HR, 4.3) were identified as independent risk factors. Lung injury-free time was shorter in patients with low initial Pao(2)/Fio(2) ratio (odds ratio, 1.7; P = .039). This effect was not only caused by the baseline difference, as the decrease in Pao(2)/Fio(2) ratio was more pronounced in patients who developed lung injury compared to those who did not (P = .008). CONCLUSIONS: Lung injury exacerbates during mechanical ventilation. In patients treated with a mean tidal volume of 7.9 mL/kg, controlled ventilation is a major risk factor.

A single recruitment maneuver in ventilated critically ill children can translocate pulmonary cytokines into the circulation.

INTRODUCTION: Recruitment maneuvers (RMs) are advocated to prevent pulmonary collapse during low tidal volume ventilation and improve oxygenation. However, convincing clinical evidence for improved outcome is lacking. Recent experimental studies demonstrate that RMs translocate pulmonary inflammatory mediators into the circulation. To determine whether a single RM in ventilated children affects pulmonary and systemic cytokine levels, we performed a prospective intervention study. METHODS: Cardiorespiratory stable ventilated patients (0.5-45 months, n = 7) with acute lung injury were subjected to an RM determining opening and closing pressures (peak inspiratory pressure < or =45 cmH(2)O, positive end expiratory pressure (PEEP) < or =30 cmH(2)O). Before and after RM, cardiorespiratory parameters and ventilator settings were recorded, blood gas analysis performed, and bronchoalveolar lavage fluid and plasma TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 concentrations were determined. RESULTS: Fifteen minutes after the RM, an increase was observed in plasma tumor necrosis factor-alpha (400% +/- 390% of baseline, P = .04), IL-6 (120% +/- 35%, P = .08), and IL-1beta (520% +/- 535%, P = .04), which decreased at T = 60 minutes, hence indicative of translocation. Recruitment maneuver did not change the plasma levels of the anti-inflammatory IL-10 (105% +/- 12%, P = .5). Apart from a nonsignificant increase of IL-8 after 360 minutes (415% +/- 590%,P = .1), bronchoalveolar cytokine levels were not influenced by the RM. No increase in oxygenation or improvement of lung kinetics was observed. CONCLUSIONS: A single RM can translocate pro-inflammatory cytokines from the alveolar space into the systemic circulation in ventilated critically ill children.

Failed resuscitation of a newborn due to congenital tracheal agenesis: a case report.

Tracheal agenesis is a rare congenital condition. It usually presents as an unexpected emergency during resuscitation of a newborn in the delivery room. The condition is almost always fatal in the resuscitation phase, but also when the neonate survives the long term prognosis remains poor. We present a case of tracheal agenesis, discuss its presenting symptoms and possibilities for antenatal diagnosis and review the therapeutic options.

Mechanical ventilation induces a Toll/interleukin-1 receptor domain-containing adapter-inducing interferon beta-dependent inflammatory response in healthy mice.

BACKGROUND: Mechanical ventilation (MV) can induce lung injury. Proinflammatory cytokines have been shown to play an important role in the development of ventilator-induced lung injury. Previously, the authors have shown a role for Toll-like receptor 4 signaling. The current study aims to investigate the role of Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-beta (TRIF), a protein downstream of Toll-like receptors, in the development of the inflammatory response after MV in healthy mice. METHODS: Wild-type C57BL6 and TRIF mutant mice were mechanically ventilated for 4 h. Lung tissue and plasma was used to investigate changes in cytokine profile, leukocyte influx, and nuclear factor-kappaB activity. In addition, experiments were performed to assess the role of TRIF in changes in cardiopulmonary physiology after MV. RESULTS: MV significantly increased messenger RNA expression of interleukin (IL)-1beta in wild-type mice, but not in TRIF mutant mice. In lung homogenates, MV increased levels of IL-1alpha, IL-1beta, and keratinocyte-derived chemokine in wild-type mice. In contrast, in TRIF mutant mice, only a minor increase in IL-1beta and keratinocyte-derived chemokine was found after MV. Nuclear factor-kappaB activity after MV was significantly lower in TRIF mutant mice compared with wild-type mice. In plasma, MV increased levels of IL-6 and keratinocyte-derived chemokine. In TRIF mutant mice, no increase of IL-6 was found after MV, and the increase in keratinocyte-derived chemokine appeared less pronounced. TRIF deletion did not affect cardiopulmonary physiology after MV. CONCLUSIONS: The current study supports a prominent role for TRIF in the development of the pulmonary and systemic inflammatory response after MV.

A case of juvenile bullous pemphigoid--successful treatment with diaminodiphenylsulfone and prednisone.

Blistering skin diseases can be difficult to diagnose, particularly in children. Because of the wide variety of bullous disorders and the considerable clinical overlap between them, it is difficult to differentiate one from the other on clinical features alone. Appropriate additional investigations are required to confirm the diagnosis. These include routine histologic examination of the skin, in addition to immunohistochemical staining and immune serology. Here, we present a rare case of juvenile bullous pemphigoid, which we will use to illustrate the difficulties encountered in the diagnostic process and to show how acquired blistering disorders of childhood should be approached.

The oxygenation ratio during mechanical ventilation in children: the role of tidal volume and positive end-expiratory pressure.

OBJECTIVE: The objective of this study is to analyze the role of tidal volume (Vt) and positive end-expiratory pressure on the oxygenation ratio (OR) (Pao(2)/Fio(2)) during mechanical ventilation (MV) in children with a normal pulmonary gas exchange on admission. METHODS: A retrospective cohort study of children with an admission OR greater than 300 mm Hg and duration of MV greater than 48 hours (n = 96) was done. We analyzed Vt, Fio(2), Pao(2), and positive end-expiratory pressure and calculated Vt (mL/kg) and Pao(2)/Fio(2) based on the measured Vt and weight. Patients were divided into group 1, Vt less than 9 mL/kg (n = 24); 2, Vt 9 to 12 mL/kg (n = 58); and 3, Vt 12 mL/kg or higher (n = 14). RESULTS: Baseline characteristics and OR were comparable. Forty-one percent of patients developed OR less than 300 mm Hg. The proportion of patients developing an OR less than 300 mm Hg was lowest in group 1 and highest in group 3, and differences became more pronounced with longer MV duration: 56%, 58%, and 89% on day 5; 29%, 65%, and 100% on day 7 (P = .05); 0%, 40%, and 100% on day 10 (P = .03). In patients maintaining an OR greater than 300 mm Hg during 10 days of MV, Vt was 9.3 +/- 1.0 vs 12.7 +/- 4.8 mL/kg in patients developing an OR less than 300 mm Hg (P = .05). Mechanical ventilation duration was longer in children developing OR less than 300 mm Hg (P < .01). Positive end-expiratory pressure levels were not significantly different between groups. CONCLUSION: In ventilated children, Vt was greater than 9 mL/kg were associated with increased development of an OR less than 300 mm Hg and longer duration of MV.

Low-tidal-volume mechanical ventilation induces a toll-like receptor 4-dependent inflammatory response in healthy mice.

BACKGROUND: Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. METHODS: Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. RESULTS: MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of keratinocyte-derived chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in keratinocyte-derived chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, keratinocyte-derived chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of keratinocyte-derived chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. CONCLUSIONS: The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.

Hypercapnic acidosis attenuates the pulmonary innate immune response in ventilated healthy mice.

BACKGROUND: Mechanical ventilation with small tidal volumes reduces the development of ventilator-induced lung injury and mortality, but may increase PaCO2. It is not clear whether the beneficial effect of a lung-protective strategy results from reduced ventilation pressures/tidal volumes or is mediated by the effects of hypercapnic acidosis on the inflammatory response involved in the pathogenesis of ventilator-induced lung injury. OBJECTIVE: To analyze whether hypercapnic acidosis affects lung tissue cytokine levels and leukocyte influx in healthy ventilated mice. STUDY DESIGN: Analysis of lung tissue and plasma concentrations of interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and keratocyte-derived chemokine after 2 hrs of mechanical ventilation (V(t) 8 mL/kg, positive end-expiratory pressure 4 cm H2O) with 0.06% CO2 (room air), 2% CO2, or 4% CO2. SUBJECTS: Healthy C57BL6 mice (n = 40). MEASUREMENTS/RESULTS: PaCO2 and pH were within normal range when ventilated with 0.06% CO2 and significantly changed with 2% and 4% CO2: (mean +/- SD) pH 7.23 +/- 0.06 and 7.15 +/- 0.04, PaCO2 7.9 +/- 1.4 and 10.8 +/- 0.7 kPa, respectively (p < 0.005). Blood pressure remained within normal limits in all animals. Quantitative microscopic analysis showed a 4.7 +/- 3.7-fold increase (p < 0.01) in pulmonary leukocyte influx in normocapnic ventilated animals and a significant reduction in leukocyte influx of 57 +/- 32% (p < 0.01) and 67 +/- 22% (p < 0.01) when ventilated with 2% and 4% CO2, respectively. Normocapnic ventilation induced a significant elevation of lung tissue IL-1beta (1516 +/- 119 ng/mL), TNF-alpha (344 +/- 88 ng/mL), IL-6 (6310 +/- 807 ng/mL), IL-10 (995 +/- 152 ng/mL), and keratocyte-derived chemokine (36,966 +/- 15,294 ng/mL) (all p-values <0.01). Hypercapnic acidosis with 2% respectively 4% CO2 significantly attenuated this increase with 25 +/- 32% and 54 +/- 32% (IL-1beta, p < 0.01); 17 +/- 36% and 58 +/- 33% (TNF-alpha, p < 0.02); 22 +/- 34% and 89 +/- 6% (IL-6, p < 0.01); 20 +/- 31% and 67 +/- 17% (IL-10, p < 0.01) and 16 +/- 44% and 45 +/- 30% (keratocyte-derived chemokine, p = 0.07). CONCLUSION: Hypercapnic acidosis attenuates the mechanical ventilation-induced immune response independent from reduced tidal volumes/pressures and may protect the lung from ventilator induced lung injury.

Mechanical ventilation in healthy mice induces reversible pulmonary and systemic cytokine elevation with preserved alveolar integrity: an in vivo model using clinical relevant ventilation settings.

BACKGROUND: Mechanical ventilation (MV) may activate the innate immune system, causing the release of cytokines. The resulting proinflammatory state is a risk factor for ventilator-induced lung injury. Cytokine increase results from direct cellular injury but may also result from cyclic stretch alone as demonstrated in vitro: mechanotransduction. To study mechanotransduction in vivo, the authors used an animal MV model with clinically relevant ventilator settings, avoiding alveolar damage. METHODS: Healthy C57BL6 mice (n = 82) were ventilated (tidal volume, 8 ml/kg; positive end-expiratory pressure, 4 cm H2O; fraction of inspired oxygen, 0.4) for 30, 60, 120, and 240 min. Assigned animals were allowed to recover for 2 days after MV. Both pulmonary tissue and plasma interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor alpha, IL-6, IL-10, and keratinocyte-derived chemokine levels were measured. Histopathologic appearance of lung tissue was analyzed by light microscopy and electron microscopy. RESULTS: In lung tissue, all measured cytokines and keratinocyte-derived chemokine levels increased progressively with MV duration. Light microscopy showed increased leukocyte influx but no signs of alveolar leakage or albumin deposition. Electron microscopy revealed intact epithelial cell and basement membranes with sporadically minimal signs of partial endothelial detachment. In plasma, increased levels of IL-1alpha, tumor necrosis factor alpha, IL-6, and keratinocyte-derived chemokine were measured after MV. In the recovery animals, cytokine levels had normalized and no histologic alterations could be found. CONCLUSIONS: Mechanical ventilation induces reversible cytokine increase and leukocyte influx with preserved tissue integrity. This model offers opportunities to study the pathophysiologic mechanisms behind ventilator-induced lung injury and the contribution of MV to the "multiple-hit" concept.