Acute cortisol release during stereotactic fractionated radiotherapy to an ACTH-secreting pituitary macroadenoma.

A 33-year old male was diagnosed with Cushing's disease due to a large and invasive ACTH-secreting macroadenoma. After surgical failure ketoconazole therapy was initiated to control cortisol hypersecretion and his symptoms. He was referred to radiotherapy, and fractionated stereotactic radiotherapy in 30 fractions was delivered. After 12 daily fractions of radiotherapy the urinary cortisol release increased abruptly together with clinical deterioration. The daily ketoconazole dose was increased, and 10 days after concluding radiotherapy his urinary cortisol returned to normal values. Hormonal remission was observed less than 1 year following radiotherapy.

Ventilation index and outcome in children with acute respiratory distress syndrome.

The purpose of this investigation was to determine the predictive value of the ventilation index (VI) in children with acute respiratory distress syndrome (ARDS). We performed a 10-year retrospective chart review of children who were admitted to the Pediatric Intensive Care Unit with a diagnosis of ARDS. Acute respiratory distress syndrome was defined as acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin, and severe hypoxemia, defined as the ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen of <200 and a positive end expiratory pressure of 6 cmH2O or greater. Records of daily arterial blood gas results and ventilator settings were reviewed, and the ventilation index (VI=partial pressure of arterial CO2 x peak airway pressure x respiratory rate/1,000) was calculated each time the measurements were made. These values were correlated with outcome (survival or nonsurvival). The VI was not different at the time of diagnosis of ARDS in the patients who lived, compared with those who subsequently died. However, by 3 to 5 days after study entry, the VI of nonsurvivors was significantly higher than for survivors (P < 0.05). The VI for survivors remained between 30 and 35 throughout the study period, whereas the VI of nonsurvivors continued to increase with time. A VI of >65 predicted death with a specificity and positive predictive value of >90% on days 3 through 9. We conclude that the VI provides a reliable prognostic marker in children with ARDS, and its increase above 65 indicates a need for orderly intervention with alternative modalities of care.

Acute respiratory distress syndrome in children: a 10 year experience.

BACKGROUND: Acute respiratory distress syndrome is a well-recognized condition resulting in high permeability pulmonary edema associated with a high morbidity. OBJECTIVES: To examine a 10 year experience of predisposing factors, describe the clinical course, and assess predictors of mortality in children with this syndrome. METHODS: The medical records of all admissions to the pediatric intensive care unit over a 10 year period were evaluated to identify children with ARDS. Patients were considered to have ARDS if they met all of the following criteria: acute onset of diffuse bilateral pulmonary infiltrates of non-cardiac origin and severe hypoxemia defined by < 200 partial pressure of oxygen during > or = 6 cm H2O positive end-expiratory pressure for a minimum of 24 hours. The medical records were reviewed for demographic, clinical, and physiologic information including PaO2/forced expiratory O2, alveolar-arterial O2 difference, and ventilation index. RESULTS: We identified 39 children with the adult respiratory distress syndrome. Mean age was 7.4 years (range 50 days to 16 years) and the male:female ratio was 24:15. Predisposing insults included sepsis, pneumonias, malignancy, major trauma, shock, aspiration, near drowning, burns, and envenomation. The mortality rate was 61.5%. Predictors of death included the PaO2/FIO2, ventilation index and A-aDO2 on the second day after diagnosis. Nonsurvivors had significantly lower PaO2/FIO2 (116 +/- 12 vs. 175 +/- 8.3, P < 0.001), and higher A-aDO2 (368 +/- 28.9 vs. 228.0 +/- 15.5, P < 0.001) and ventilation index (43.3 +/- 2.9 vs. 53.1 +/- 18.0, P < 0.001) than survivors. CONCLUSIONS: Local mortality outcome for ARDS is comparable to those in tertiary referral institutions in the United States and Western Europe. The PaO2/FIO2, A-aDO2 and ventilation index are valuable for predicting outcome in ARDS by the second day of conventional therapy. The development of a local risk profile may allow early application of innovative therapies in this population.

[Head injuries in children--clinical characteristics as prognostic factors].

An unselected series of 200 consecutive cases of major head trauma in children aged 6 months to 16 years, seen during 4 years, was studied. Injuries were due to road accidents (40%), falls (30.5%) and other causes (29.5%), and were assessed clinically and by cranial CT. On admission the Glasgow Coma Score ranged from 4.72-11.65 and in addition to pupillary responses and brain stem reflexes, was a significant predictor of outcome. Brain edema, midline shift, intracranial hemorrhage and also hyperglycemia, hypokalemia and coagulopathy, were associated with poor outcome. While 17% died, 53% were discharged in good functional condition. Early identification of clinical features related to prognosis can help the caring team provide maximal support for patient and family.

Pharmacokinetics of endobronchial tolazoline administration in dogs.

Tolazoline is a potent vasodilator of arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in the systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endobronchial tolazoline to determine the relationship between endobronchial tolazoline administration, plasma concentration, and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endobronchially to seven dogs, and its serum concentration and the hemodynamic parameters were monitored for 270 min postdelivery. It was found that 15 sec after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 9.3+/-8.0 microg x mL(-1) The volume of distribution was 1657+/-321 mL x kg(-1) after 1 2.4+/-1 6.6 min. The extent of tolazoline absorption was 319+/-38 microg x min(-1) mL(-1). The total body clearance was 10.9 +/-4.8 mL x min(-1) x Kg(-1) and the elimination half-life was 156+/-81 min. Endobronchial tolazoline produced an initial short-lived decrease in the mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endobronchial tolazoline a significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. We conclude that an endobronchial bolus dose of tolazoline is effectively absorbed, produces measurable pharmacological effects, and may be beneficial in the therapy of persistent pulmonary hypertension of the newborn.

Is endotracheal adrenaline deleterious because of the beta adrenergic effect?

IV adrenaline increases coronary and cerebral perfusion pressures during cardiopulmonary resuscitation. We recently showed that endotracheal adrenaline can decrease blood pressure (BP), a detrimental effect presumably mediated by the beta 2-adrenergic receptor unopposed by alpha-adrenergic vasoconstriction. This prospective, randomized, laboratory comparison of endotracheal adrenaline (0.05 mg/kg diluted with normal saline to 10 mL total volume) with or without nonselective beta-blocker (propranolol) pretreatment was conducted in an attempt to clarify the mechanism of this BP decrease. Five mongrel dogs were given 0.05 mg/kg endotracheal adrenaline (diluted) or 0.05 mg/kg endotracheal adrenaline followed by an IV propranolol (0.1 mg/kg) pretreatment. Each dog served as its own control (10 mL of normal saline administered endotracheally) and received each regimen at least one week apart. Endotracheal adrenaline given after the propranolol pretreatment produced an increase in systolic, diastolic, and mean arterial BPs, from 165/110 mm Hg (mean 128 mm Hg) to 177.5/125 mm Hg (mean 142.5 mm Hg), respectively, as opposed to the hypotensive effect of isolated endotracheal adrenaline (P < 0.03). Thus, endotracheal adrenaline was associated with predominantly beta-adrenergic-mediated effects, causing hypotension via peripheral vasodilatation unopposed by alpha-adrenergic vasoconstriction. The search for the optimal dose of endotracheal adrenaline should be aimed at achieving the higher alpha-adrenergic vasoconstrictive threshold.