Use of bilevel positive airway pressure (BIPAP) in end-stage patients with cystic fibrosis awaiting lung transplantation.

Nine consecutive end-stage patients with cystic fibrosis (CF) awaiting lung transplantation were admitted to the pediatric intensive care unit (PICU) in respiratory decompensation. They all received noninvasive bilevel positive airway pressure (BIPAP) support and were evaluated to determine whether or not it improved their oxygenation and provided them with long-term respiratory stability. BIPAP was applied to all patients after a brief period of assessment of their respiratory status. Inspiratory and expiratory positive airway pressures (IPAP, EPAP) were initially set at 8 and 4 cm H2O respectively. IPAP was increased by increments of 2 cm H2O and EPAP was increased by 1 cm H2O increments until respiratory comfort was achieved and substantiated by noninvasive monitoring. Patients were observed in the PICU for 48 to 72 hours and then discharged to home with instructions to apply BIPAP during night sleep and whenever subjectively required. Regular follow-up visits were scheduled through the hospital-based CF clinic. The patients' final IPAP and EPAP settings ranged from 14 to 18 cm H2O and 4 to 8 cm H2O, respectively. All nine patients showed a marked improvement in their respiratory status with nocturnal use of BIPAP at the time of discharge from the PICU. Their oxygen requirement dropped from a mean of 4.6 +/- 1.1 L/min to 2.3 +/- 1.5 L/min (P < 0.05). Their mean respiratory rate decreased from 34 +/- 4 to 28 +/- 5 breaths per minute (P < 0.05). The oxygen saturation of hemoglobin measured by pulse oximetry, significantly increased from a mean of 80% +/- 15% to 91% +/- 5% (P < 0.05). The patients have been followed up for a period of 2 to 43 months and have all tolerated the use of home nocturnal BIPAP without any reported discomfort. Six patients underwent successful lung transplantation after having utilized nocturnal BIPAP for 2, 6, 14, 15, 26, and 43 months, respectively. Three patients have utilized home BIPAP support for 2, 3, and 19 months, respectively, and continue to await lung transplantation. An acute development of refractory respiratory failure resulted in the demise of the remaining three patients after having utilized BIPAP for 3, 6, and 10 months, respectively. The authors conclude that BIPAP therapy improves the respiratory status of decompensating end-stage CF patients. It is well tolerated for long-term home use and provides an extended period of respiratory comfort and stability for CF patients awaiting lung transplantation.

A comparison among animal models of acute lung injury.

OBJECTIVES: To compare four widely used animal models of acute lung injury and to determine the changes in physiologic variables associated with each model. DESIGN: A prospective, controlled animal study. SETTING: An animal laboratory of a university-affiliated children's hospital. SUBJECTS: Four groups of anesthetized, paralyzed, and ventilated young Yorkshire pigs, weighing 35 to 45 kg. INTERVENTIONS: Acute lung injury was generated by four different methods: a) intrapulmonary arterial infusion of endotoxin of Escherichia colt; b) bronchoalveolar instillation of 0.05N of hydrochloric acid; c) repeated bronchoalveolar warm saline lavage; and d) intrapulmonary arterial infusion of oleic acid. After each acute lung injury procedure, the temporal changes in various physiologic variables were measured, starting at 60 mins and at 15-min intervals thereafter for a total of 165 mins. Systemic and mixed venous serum immunoreactive tumor necrosis factor (TNF)-alpha concentrations were also measured at the same time points. Analysis of variance for repeated measures was employed to determine the absolute and relative significance of the changes observed. MEASUREMENTS AND MAIN RESULTS: Systemic and mixed venous immunoreactive TNF-alpha did not change following any of the acute lung injury procedures. The animals' heart rates and systemic vascular resistances also did not change. Hydrochloric acid instillation as well as bronchoalveolar lavage resulted in significant hypoxemia with no other hemodynamic effects. Endotoxin infusion did not result in hypoxemia but caused significant increases in mean pulmonary arterial pressure and pulmonary vascular resistance and decreases in mean arterial pressure and cardiac output. Oleic acid infusion resulted in a marked hypoxemia with a pronounced increase in mean pulmonary arterial pressure and pulmonary vascular resistance. It also markedly reduced the mean arterial pressure, cardiac output, and the mixed venous PO2. CONCLUSIONS: The surfactant depletion and hydrochloric acid instillation models produce acute hypoxemia in an otherwise hemodynamically stable animal. A brief endotoxin infusion provides a model for cardiovascular instability and pulmonary hypertension but fails to produce hypoxemia in the pig. The oleic acid infusion creates a model of marked cardiovascular instability, pulmonary hypertension, and profound hypoxemia. However, none of the acute lung injury models described was associated with the production of tumor necrosis factor.

Increased artificial deadspace ventilation is a safe and reliable method for deliberate hypercapnia.

OBJECTIVES: To develop a simple method in an animal model to achieve deliberate hypercapnia, which can be used easily and safely to regulate the pulmonary vascular resistance without changing mean airway pressure and compromising oxygenation. DESIGN: Prospective study, with each animal used as its own control. SUBJECTS: Minipigs, weighing 11 to 14 kg (n = 7). INTERVENTIONS: A quadrilumen thermodilution pulmonary artery catheter was placed in minipigs via the internal jugular vein. Systemic blood pressure was measured with use of a femoral arterial catheter. The animals' lungs were ventilated with an FIO2 of 1.0, and a stable state of eucapnia was achieved and maintained for 30 mins. The artificial deadspace was increased every 30 mins, by connecting 45-mL (3- to 4-mL/kg) corrugated tube segments until a total deadspace volume of 180 mL was added. MEASUREMENTS AND MAIN RESULTS: Hemodynamic performance was evaluated at baseline and after 45 mL (3 to 4 mL/kg), 90 mL (6 to 8 mL/kg), 135 mL (9 to 11 mL/kg), and 180 mL (12 to 15 mL/kg) of added deadspace. Data were indexed to the animal's weight (in kg). Increased artificial deadspace produced a significant (p < .05) increase in PaCO2. These increases in PaCO2 were associated with significant (p < .05) increases of 23%, 32%, 45%, and 46% in the mean pulmonary vascular resistance values, and 6%, 16%, 23%, and 23% in the mean pulmonary arterial pressure, respectively. The systemic pH was decreased from a mean baseline value of 7.45 to 7.39, 7.28, 7.20, and 7.11, respectively. There were no significant changes in PaO2, oxygen consumption, systemic vascular resistance, and cardiac output throughout the experiments. CONCLUSIONS: A gradual increase in artificial deadspace ventilation produces a state of deliberate hypercapnia. In our animal model, a moderate increase in artificial deadspace significantly increased the pulmonary vascular resistance but was not associated with detrimental respiratory acidemia. Larger volumes of added artificial deadspace had no detrimental effect on cardiac output, oxygen content, oxygen consumption, and systemic vascular resistance, but were associated with significant respiratory acidemia and therefore should be avoided.

Diagnosis and management algorithm of acute onset of central diabetes insipidus in critically ill children.

We devised a diagnosis and management algorithm for acute onset of central diabetes insipidus (CDI), and conducted a retrospective evaluation of its efficacy. Fourteen patients admitted to our pediatric intensive care unit (PICU) over a three year period were diagnosed with acute CDI secondary to various brain injuries. All patients were treated as per the algorithm guidelines. The initial dose of aqueous vasopressin ranged from 0.25 to 1.0 mU/kg/h. Low sodium content solution (0-0.5 normal saline) was used to replace urine output in excess of 3 ml/kg/h and for maintenance fluid therapy. The therapeutic goals included: urine output 2-3 ml/kg/h, urine specific gravity 1.010-1.020 and serum sodium 140-145 mEq/l. The pitressin dose was adjusted as deemed necessary to achieve the aforementioned goals. Our results indicate that urine specific gravity is the most sensitive parameter to respond to treatment. It was the best determinant of the adequacy of pitressin dose as it had the best linear correlation with it (r = 0.96; p = 0.009). Urine output was second best (r = 0.93; p = 0.02), whereas no linear correlation was established between pitressin dose and serum sodium concentration, nor with serum osmolality. We conclude that the algorithm developed and used by us for the management of CDI is generally efficacious. Changes in urine specific gravity follow changes in pitressin dose very closely and thus should be used as the primary parameter for determination of intravenous pitressin dose adjustment.