Correlation between alveolar recruitment/derecruitment and inflection points on the pressure-volume curve.

OBJECTIVE: To determine whether individual alveolar recruitment/derecruitment (R/D) is correlated with the lower and upper inflections points on the inflation and deflation limb of the whole-lung pressure-volume (P-V) curve. DESIGN AND SETTING: Prospective experimental study in an animal research laboratory. SUBJECTS: Five anesthetized rats subjected to saline-lavage lung injury. INTERVENTIONS: Subpleural alveoli were filmed continuously using an in vivo microscope during the generation of a whole-lung P-V curve using the super syringe technique. Alveolar R/D was correlated to the calculated inflection points on both limbs of the P-V curve. MEASUREMENTS AND RESULTS: There was continual alveolar recruitment along the entire inflation limb in all animals. There was some correlation (R2=0.898) between the pressure below which microscopic derecruitment was observed and the upper inflection point on the deflation limb. No correlation was observed between this pressure and the lower inflection point on the inflation limb. CONCLUSIONS: In this physiological experiment in lungs with pure surfactant deactivation we found that individual alveolar recruitment measured by direct visualization was not correlated with the lower inflection point on inflation whereas alveolar derecruitment was correlated with alveolar derecruitment on deflation. These data suggest that inflection points on the P-V curve do not always represent a change in alveolar number.

Absence of alveolar tears in rat lungs with significant alveolar instability.

BACKGROUND: Lung injury associated with the acute respiratory distress syndrome can be exacerbated by improper mechanical ventilation creating a secondary injury known as ventilator-induced lung injury (VILI). We hypothesized that VILI could be caused in part by alveolar recruitment/derecruitment resulting in gross tearing of the alveolus. OBJECTIVES: The exact mechanism of VILI has yet to be elucidated though multiple hypotheses have been proposed. In this study we tested the hypothesis that gross alveolar tearing plays a key role in the pathogenesis of VILI. METHODS: Anesthetized rats were ventilated and instrumented for hemodynamic and blood gas measurements. Following baseline readings, rats were exposed to 90 min of either normal ventilation (control group: respiratory rate 35 min(-1), positive end-expiratory pressure 3 cm H(2)O, peak inflation pressure 14 cm H(2)O) or injurious ventilation (VILI group: respiratory rate 20 min(-1), positive end-expiratory pressure 0 cm H(2)O, peak inflation pressure 45 cm H(2)O). Parameters studied included hemodynamics, pulmonary variables, in vivo video microscopy of alveolar mechanics (i.e. dynamic alveolar recruitment/derecruitment) and scanning electron microscopy to detect gross tears on the alveolar surface. RESULTS: Injurious ventilation significantly increased alveolar instability after 45 min and alveoli remained unstable until the end of the study (electron microscopy after 90 min revealed that injurious ventilation did not cause gross tears in the alveolar surface). CONCLUSIONS: We demonstrated that alveolar instability induced by injurous ventilation does not cause gross alveolar tears, suggesting that the tissue injury in this animal VILI model is due to a mechanism other than gross rupture of the alveolus.

Dynamic alveolar mechanics in four models of lung injury.

OBJECTIVE: To determine whether pathological alterations in alveolar mechanics (i.e., the dynamic change in alveolar size and shape with ventilation) at a similar level of lung injury vary depending on the cause of injury. DESIGN AND SETTING: Prospective controlled animal study in a university laboratory. SUBJECTS: 30 male Sprague-Dawley rats (300-550 g). INTERVENTIONS: Rats were separated into one of four lung injury models or control (n=6): (a) 2% Tween-20 (Tween, n=6), (b) oleic acid (OA, n=6), (c) ventilator-induced lung injury (VILI, PIP 40/ZEEP, n=6), (d) endotoxin (LPS, n=6). Alveolar mechanics were assessed at baseline and after injury (PaO2/FIO2 <300 mmHg) by in vivo microscopy. MEASUREMENTS: Alveolar instability (proportional change in alveolar size during ventilation) was used as a measurement of alveolar mechanics. RESULTS: Alveoli were unstable in Tween, OA, and VILI as hypoxemia developed (baseline vs. injury: Tween, 7+/-2% vs. 67+/-5%; OA: 3+/-2% vs. 82+/-9%; VILI, 4+/-2% vs. 72+/-5%). Hypoxemia after LPS was not associated with significant alveolar instability (baseline vs. injury: LPS, 3+/-2 vs. 8+/-5%). CONCLUSIONS: These data demonstrate that multiple pathological changes occur in dynamic alveolar mechanics. The nature of these changes depends upon the mechanism of lung injury.

Appendicitis in childhood hematologic malignancies: analysis and comparison with typhilitis.

BACKGROUND/PURPOSE: Recognition of appendicitis in the child with hematologic malignancy may be difficult particularly in the setting of neutropenia and multiple medications causing an altered inflammatory response. Typhilitis may produce a similar constellation of clinical findings causing further diagnostic confusion. This review compares the relative frequency of these two conditions in children with hematologic malignancy with a focus on the clinical presentation, distinguishing features, surgical management, and outcome for patients with appendicitis. METHODS: This institutional review board-approved retrospective study evaluated 464 pediatric patients treated for hematologic malignancy at our institution from 1997 to 2003. From this cohort, we identified all children with a diagnosis of appendicitis or typhilitis. Data include demographics, clinical presentation, laboratory studies, and computed tomography (CT) scan findings. Groups were compared using the Fisher exact test. Significance was defined as P < .05. RESULTS: Eight (1.7%) of 464 children were diagnosed with typhilitis and 7 (1.5%) with appendicitis. There were no demographic differences between patients with appendicitis and typhilitis. Distinguishing clinical features in children with typhilitis included presence of fever and diarrhea. Clinical presentation in children with appendicitis was atypical in 5 of 7 cases yielding an incorrect preoperative diagnosis in all 5. Radiographic evaluation by CT scan accurately defined typhilitis, but not appendicitis. An operation was performed on all 7 children with appendicitis with no operative morbidity or mortality. CONCLUSIONS: Appendicitis and typhilitis occur with similar frequency in children with leukemia and lymphoma. Typhilitis is accurately diagnosed with clinical findings of fever, diarrhea, abdominal pain, and typical CT scan findings. Appendicitis tends to present with atypical findings, but can be successfully managed with standard surgical care.

Predictors of successful outcome after cholecystectomy for biliary dyskinesia.

PURPOSE: Laparoscopic cholecystectomy is accepted therapy for children with ill-defined abdominal pain and impaired gallbladder emptying (biliary dyskinesia). Follow-up shows poor clinical response in many of these patients. The purpose of this report is to identify clinical and radiographic predictors of successful outcome after cholecystectomy for biliary dyskinesia. METHODS: The authors retrospectively reviewed records of 51 children after laparoscopic cholecystectomy for biliary dyskinesia (1990 to 2003). Clinical symptoms, radiographic findings, and pathology were evaluated. Subjective clinical improvement is stratified using an established patient satisfaction score. Logistic regression analysis determines statistically independent predictors of successful outcome. RESULTS: Thirty-eight of 51 (75%) patients were available for follow-up. Twenty-seven of 38 (71%) patients reported complete resolution of symptoms. Nausea was the only symptom predictive of successful outcome by univariate analysis (odds ratio, 5.00). A cholecystokinin-stimulated, gallbladder ejection fraction less than 15% also predicts successful outcome (odds ratio, 8.00). Children with an ejection fraction greater than 15% did not have predictable resolution of symptoms. When present with pain and nausea, gallbladder emptying less than 15% has a positive predictive value of 93% and a negative predictive value of 81%. CONCLUSIONS: Together, nausea, pain, and decreased gallbladder emptying (<15%) most reliably predict which children will benefit from cholecystectomy for biliary dyskinesia.

Alveolar mechanics alter hypoxic pulmonary vasoconstriction.

OBJECTIVES: Hypoxic pulmonary vasoconstriction is the primary physiologic mechanism that maintains a proper ventilation/perfusion match, but it fails in diffuse lung injuries such as acute respiratory distress syndrome. Acute respiratory distress syndrome is associated with pulmonary surfactant loss that alters alveolar mechanics (i.e., dynamic change in alveolar size and shape during ventilation), converting normal stable alveoli into unstable alveoli. We hypothesized that alveolar instability stents open pulmonary microvessels and is the mechanism of hypoxic pulmonary vasoconstriction failure associated with acute respiratory distress syndrome. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Ten adult pigs. INTERVENTIONS: Anesthetized ventilated pigs were prepared surgically for hemodynamic monitoring and were subjected to a right thoracotomy. An in vivo microscope was attached to the right lung, and the microvascular response to hypoxia (F(IO(2)), 15%) was measured in a lung with normal stable alveoli and in a lung with unstable alveoli caused by surfactant deactivation (Tween lavage). MEASUREMENTS AND MAIN RESULTS: Alveolar instability, defined as the difference between alveolar area at peak inspiration and end expiration and assessed as a percentage change (I-E Delta%), was significantly increased after Tween (23.9 +/- 3.0, I-E Delta%) compared with baseline (2.4 +/- 1.0, I-E Delta%). Alveolar instability was associated with the following microvascular changes: a) increased vasoconstriction (Tween, 14.9 +/- 1.0%) in response to hypoxia compared with baseline (10.8 +/- 1.2%, p <.05); and b) increased mean vascular diameter (Tween, 41.2 +/- 1.5 microm) compared with the mean diameter at baseline (24.6 +/- 1.0 microm, p <.05). CONCLUSION: Unstable alveoli stent open pulmonary vessels, which may explain the failure of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome.