Faculty Bibliography

Objective: Diphenhydramine is a common over-the-counter antihistamine which rarely leads to severe toxicity. We report a patient with a diphenhydramine overdose manifested with seizure and cardiac arrest. Though her hemodynamics improved with VA-ECMO and hydroxocobalamin, the patient was ultimately declared brain dead and underwent organ procurement. Case report: A 34-year-old woman with a history of depression was found by emergency medical services with seven bottles of diphenhydramine, two of which were empty. The patient seized and moments afterwards went into cardiac arrest. Advanced cardiac life support (ACLS) was initiated, with chest compressions performed for 35 minutes, 2mg of epinephrine given intravenously, an epinephrine infusion and intubation. Additionally, the patient received intermittent boluses of sodium bicarbonate totaling 150 mEq, 25 g dextrose and 1 g calcium gluconate. Toxicology was consulted and recommended an additional 150 mEq IV bolus of sodium bicarbonate and, within 5 minutes, the patient regained a pulse. On physical exam, she had minimally reactive pupils and was unresponsive to painful stimuli. Initial laboratory findings were remarkable for a lactate of 9 mmol/L and a potassium of 2.5mmol/L. The electrocardiogram (ECG) demonstrated a QRS of 154 ms and a QTc of 463 ms and she was placed on a bicarbonate infusion. Decontamination was performed using gastric lavage and 50 g of activated charcoal. Four hours following presentation, her vasopressor requirements included: 20 mug/min epinephrine, 60 mug/min norepinephrine, 200 mug/min phenylephrine, and 0.04 U/min vasopressin. She developed acute respiratory distress syndrome (ARDS) so was placed on VA-ECMO. Given profound vasoplegic shock, she received 5 g of hydroxocobalamin and was quickly weaned off her vasopressor requirements to 5 mug/min epinephrine and 15 mug/min norepinephrine. Repeat ECG showed a QRS of 160 ms and QTc 565 ms. Her ECG normalized within 24 hours of arrival and bicarbonate infusion was discontinued. She was on VA-ECMO for seven days with stable hemodynamics, and never developed acute kidney or liver injury. She was declared brain dead on hospital day 7 and underwent organ procurement. The initial serum diphenhydramine concentration was 1,400 ng/mL (normal range 90-120 ng/mL).
Conclusion(s): We present a unique case of diphenhydramine overdose who obtained return of spontaneous circulation after ACLS and 150 mEq IV push of sodium bicarbonate, placed on VAECMO, and treated for vasoplegic shock with hydroxocobalamin. While there is increasing use of ECMO in poisoned patients, its use as a bridge to organ donation requires further ethical consideration

PURPOSE: This prospective study aimed to evaluate the use of acoustic rhinometry (AR) in pediatric obstructive sleep apnea (OSA). METHODS: Children with clinically suspected OSA underwent AR measurements followed by attended overnight polysomnography. RESULTS: Of a total of 20 subjects (13 boys, seven girls), 15 (75%) had OSA, defined as apnea-hypopnea index (AHI) greater than or equal to five events per hour of sleep, and five had primary snoring (PS). The mean AHI was 16.79 vs. 1.96 events/h. Positional changes in airway measurement by AR were present in the OSA group, with an average decrease in nasal cavity volume from upright to supine position of 1.53 cm(3) (p = 0.027). These changes were predictive of sleep apnea (r (2) = 0.65, p = 0.035). CONCLUSIONS: This study demonstrates a marked difference between OSA and PS groups during AR measurements of the nasopharynx. Positional airway changes had been previously reported in adults with OSA and further evaluation of the airway function in pediatric OSA is warranted

RATIONALE: In experimental models, lung fibrosis is dependent on transforming growth factor (TGF)-beta signaling. TGF-beta is secreted in a latent complex with its propeptide, and TGF-beta activators release TGF-beta from this complex. Because the integrin alpha(v)beta6 is a major TGF-beta activator in the lung, inhibition of alpha(v)beta6-mediated TGF-beta activation is a logical strategy to treat lung fibrosis. OBJECTIVES: To determine, by genetic and pharmacologic approaches, whether murine radiation-induced lung fibrosis is dependent on alpha(v)beta6. METHODS: Wild-type mice, alpha(v)beta6-deficient (Itgb6-/-) mice, and mice heterozygous for a Tgfb1 mutation that eliminates integrin-mediated activation (Tgfb1(+/RGE)) were exposed to 14 Gy thoracic radiation. Some mice were treated with an anti-alpha(v)beta6 monoclonal antibody or a soluble TGF-beta receptor fusion protein. Alpha(v)beta6 expression was determined by immunohistochemistry. Fibrosis, inflammation, and gene expression patterns were assessed 20-32 weeks postirradiation. MEASUREMENTS AND MAIN RESULTS: Beta6 integrin expression increased within the alveolar epithelium 18 weeks postirradiation, just before onset of fibrosis. Itgb6-/- mice were completely protected from fibrosis, but not from late radiation-induced mortality. Anti-alpha(v)beta6 therapy (1-10 mg/kg/wk) prevented fibrosis, but only higher doses (6-10 mg/kg/wk) caused lung inflammation similar to that in Itgb6-/- mice. Tgfb1-haploinsufficient mice were also protected from fibrosis. CONCLUSIONS: Alpha(v)beta6-mediated TGF-beta activation is required for radiation-induced lung fibrosis. Together with previous data, our results demonstrate a robust requirement for alpha(v)beta6 in distinct fibrosis models. Inhibition of alphavbeta6-mediated TGF-beta activation is a promising new approach for antifibrosis therapy

Propylthiouracil (PTU) has been held responsible for diffuse alveolar hemorrhage (DAH) with positive antineutrophil cytoplasmic antibody (ANCA) and capillaritis. We describe a case of a 23-year-old pregnant female with Grave's disease treated with PTU who presented with flu-like symptoms and progressive dyspnea. Open lung biopsy showed DAH without evidence of capillaritis. All serologies were negative. Five days after PTU withdrawal and intravenous steroid therapy, the patient improved dramatically. She remained symptom free without relapse 9 months after the episode. To the best of our knowledge, this is the first reported case of PTU-related alveolar hemorrhage with negative serologic markers and without capillaritis.

INTRODUCTION: We examined pulmonary diffusing capacity (D(LCO)) and its partition in pulmonary vascular diseases without evident parenchymal disease to assess the pattern and proportionality of change in membrane diffusion (D(m)) and capillary blood volume (V(c)). Disproportionate reduction in D(m) relative to V(c) (low D(m)/V(c)) in these diseases has been attributed to associated alveolar membrane/parenchymal disease, thus providing a potentially important diagnostic tool. METHODS: Diseases included: idiopathic pulmonary arterial hypertension (n=6), chronic thromboembolic disease (n=5), and intravenous drug use (n=14), providing a spectrum of pulmonary vascular diseases. V(c) and D(m) were determined as described by Roughton and Forster. RESULTS: All diseases showed a reduced V(c) (59+/-10, 69+/-14, 71+/-21 % predicted, respectively) and D(m) (76+/-22, 53+/-19, 63+/-16 % predicted, respectively) with no differences between groups (p>0.05). Disproportionate reduction of D(m) (D(m)/V(c) % predicted <1) was seen in all diseases (range 0.36-1.89). A mathematical analysis is presented to illustrate that changes in vascular geometry may additionally influence the proportionality of changes in D(m) and V(c). The mathematical analysis suggests that when reduction in patency of some vessels co-exits with compensatory dilatation of the remaining vasculature, a disproportionate reduction in D(m) relative to V(c) may result. CONCLUSIONS: The balance between vascular curtailment and compensatory dilatation may contribute to the variability of the D(m)/V(c) relationship seen in pulmonary vascular disease. Disproportionate reduction in D(m) relative to V(c) may result from this imbalance and need not imply subclinical alveolar membrane and/or parenchymal disease.

The diagnosis of miliary tuberculosis (TB) may be a challenging task for the physician. Pancreatitis is an extremely rare presentation of miliary TB. A healthy 31-year-old American male was admitted because of severe nausea, anorexia, malaise and night sweat for 4 days. He was febrile and his physical examination was unremarkable. The chest X-ray (CXR) was normal and the computed tomographic (CT) evaluation of the abdomen was consistent with pancreatitis. On the 12th day in the hospital, he complained of dyspnea and his chest CT showed bilateral ground-glass opacities. Subsequent bronchoscopy was not diagnostic. Open lung biopsy (OLBx) revealed multiple necrotizing granulomas. The patient responded to antituberculous therapy and was discharged home 3 weeks later. Miliary TB is a curable disease, which can take many forms. A high index of clinical suspicion and diagnostic persistence are required for diagnosis. Early diagnosis and treatment of miliary TB nurtures better outcomes