Autologous non-myeloablative hematopoietic stem cell transplantation in patients with systemic sclerosis.

Autologous hematopoietic stem cell transplantation (HSCT) utilizing a myeloablative regimen containing total body irradiation has been performed in patients with systemic sclerosis (SSc), but with substantial toxicity. We, therefore, conducted a phase I non-myeloablative autologous HSCT study in 10 patients with SSc and poor prognostic features. PBSC were mobilized with CY and G-CSF. The PBSC graft was cryopreserved without manipulation and re-infused after the patient was treated with a non-myeloablative conditioning regimen of 200 mg/kg CY and 7.5 mg/kg rabbit antithymocyte globulin. There was a statistically significant improvement of modified Rodnan skin score whereas cardiac (ejection fraction, pulmonary arterial pressure), pulmonary function (DLCO) and renal function (creatinine) remained stable without significant change. One patient with advanced disease died 2 years after the transplant from progressive disease. After median follow-up of 25.5 months, the overall and progression-free survival rates are 90 and 70% respectively. Autologous HSCT utilizing a non-myeloablative conditioning regimen appears to result in improved skin flexibility similar to a myeloablative TBI containing regimen, but without the toxicity and risks associated with TBI.

Inhaled heroin-induced status asthmaticus: five cases and a review of the literature.

We report five cases of status asthmaticus (four requiring mechanical ventilation) that were triggered by inhaled heroin and review the pertinent literature. These cases share common features of sudden and severe asthma exacerbations temporally related to heroin use, stress the importance of considering illicit drug use in like cases, and call attention to a public health issue.

Independent lung ventilation.

Situations in which independent lung ventilation may be of use include massive hemoptysis, pulmonary alveolar proteinosis, risk of interbronchial aspiration, unilateral lung injury, single lung transplant, and BPF. Any decision to attempt independent lung ventilation should take into consideration the many technical difficulties associated with the procedure. They include difficulties in the placement of DLTs and monitoring tube position, the risk of tube displacement, and the risk of airway trauma. The clinician also must consider the costs in terms of available manpower and resources. Maintaining a patient on independent lung ventilation requires highly skilled nursing care, specialized monitoring devices, and readily available FOB. Even with these limitations, independent lung ventilation may be of use in certain clinical situations when standard methods have failed.

The assessment and management of adults with status asthmaticus.

Despite advancing knowledge of the pathophysiology and treatment of asthma, asthma morbidity and mortality are on the rise. To help avert this trend, clinicians and patients must focus their attention on the early identification and treatment of asthma exacerbations. As in the words of Dr. Thomas Petty: " ... the best treatment of status asthmaticus is to treat it three days before it occurs." (7) Still, there will be asthmatics with life-threatening attacks that require careful assessment and aggressive management. Inhaled beta-agonists, systemic corticosteroids, and oxygen remain the drugs of choice in SA. Anticholinergics play a lesser role in the treatment of acute asthma, and debate continues regarding the efficacy of theophylline in this setting. Available data do not support the routine use of magnesium sulfate or antibiotics in patients with SA. Patients failing drug therapy should be considered early for intubation and mechanical ventilation. A strategy of mechanical ventilation that prolongs TE by limiting VE and decreasing inspiratory time, and that tolerates hypercapnia, avoids excessive lung hyperinflation and barotrauma and should improve the outcome of these most critically ill asthmatics. Intubated and mechanically ventilated patients should be aggressively sedated. Paralytic agents should be used only if adequate control of the cardiopulmonary status cannot be achieved by sedation alone. Minimizing the use of paralytic agents may decrease risk of myopathy and other adverse consequences of muscle paralysis. Finally, after successful treatment of a life-threatening episode of asthma, the treatment team should address prevention of future episodes of SA prior to discharge.

Management of respiratory failure in patients with asthma.

The goal of management of patients with respiratory failure is to restore them to a state of quiet breathing, without complication. This goal is often achieved by pharmacotherapy alone. Inhaled albuterol sulfate, oxygen, and systemic corticosteroids are mainstays of acute care drug management, whereas other data support the use of inhaled steroids, ipratropium bromide, magnesium sulfate, theophylline, and heliox. Assisted ventilation by face mask or endotracheal tube may be required in refractory patients. In intubated patients, a ventilatory strategy that prolongs exhalation time and accepts hypercapnia minimizes lung hyperinflation and generally results in a good outcome. Acute asthma often represents failure of outpatient management; key aspects of the outpatient program should be addressed in the acute care setting to help prevent recurrent attacks.

Techniques for ventilating patients with obstructive pulmonary disease.

In patients with obstructive lung disease, a strategy of mechanical ventilation that prolongs expiratory time and limits lung hyperinflation can decrease barotrauma. To prolong expiratory time, decrease minute ventilation and inspiratory time. Side effects of this strategy--high peak pressures and hypercapnia--are generally well tolerated. Additional goals for COPD patients include resting and strengthening respiratory muscles and decreasing load on the respiratory system. Short-acting benzodiazepines and morphine are effective for sedation and analgesia. Paralytic agents should be considered only if adequate control of the patient's cardiopulmonary status cannot be achieved by sedation alone.

Adverse effects of large tidal volume and low PEEP in canine acid aspiration.

When normal lungs are ventilated with large tidal volumes (VT) and end-inspired pressures (Pei), surfactant is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilatory with large VT-low PEEP would similarly increase edema following acute lung injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (HCl) induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 cm H2O) (large VT-low PEEP) and compared their results with dogs ventilated with a smaller VT (15 ml/kg) and 12 cm H2O PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnia in our preparation; the large VT was chosen to match Pei and end-inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) was kept at 8 mm Hg in both groups. Five hours after injury, the median lung wet weight to body weight ratio (WW/BW) was 25 g/kg higher in the large VT-low PEEP group than in the small VT-high PEEP group (p less than 0.05). Venous admixture (Qva/Qt) was similarly greater in the large VT-low PEEP group (49.8 versus 23.5%) (p less than 0.05). We conclude that small VT-high PEEP is a better mode of ventilating acute lung injury than large VT-low PEEP because edema accumulation is less and venous admixture is less. These advantages did not result from differences in Pei, end-inspiratory lung volume, or preload (Ppwtm).(ABSTRACT TRUNCATED AT 250 WORDS)