Pulmonary function of marrow transplant patients. I. Effects of marrow infusion, acute graft-versus-host disease, and interstitial pneumonitis.

The pulmonary function of patients receiving marrow transplants was studied during a two-year period. The 81 patients studied before transplantation showed a slight reduction in average lung volumes and diffusing capacity (DLCO). Studies were repeated within 48 h after marrow infusion to look for evidence of fat embolism syndrome. There was no change in the DLCO, but there was a 4% decrease in the lung volumes. Sixty-three patients (20 with aplastic anemia, 43 with hematologic malignancies) completed studies on admission and every other week during hospitalization (mean of six studies per patient). When categorized by diagnosis or conditioning regimen (including with and without total body irradiation), no differences were seen. The patients developing interstitial pneumonitis (IP) had restrictive ventilatory changes and decreases in the DLCO. The patients not developing IP remained unchanged. The patients developing IP averaged a 20% decrease in the DLCO before the clinical diagnosis of pneumonia, but a decrease in the DLCO lacked specificity for predicting occurrence of IP. Among 18 patients developing graft-versus-host disease, there was no evidence of air-flow obstruction. We conclude that patients developing IP have restrictive ventilatory changes, but in the absence of complicating IP, the marrow transplant regimen (including marrow infusion and total body irradiation) leaves pulmonary function largely unchanged.

Pulmonary function in Klinefelter's syndrome.

We evaluated pulmonary function in 24 patients with Klinefelter's syndrome. Of these, two had an obstructive defect, nine had a restrictive defect, and 11 had a decreased functional residual capacity. Since none had evidence of lung parenchymal disease, the restrictive syndrome may be due to chest wall abnormality.

Hemodynamic effects of rapid bolus hypertonic sodium bicarbonate.

We found that rapid bolus administration of hypertonic sodium bicarbonate in the recommended clinical dose produced significant, though transient, increases in intracranial pressure and decreases in blood pressure in dogs. These effects, which are related to the high osmolarity of the drug (2,000 mOsm/L), are not found when it is administered slowly.

Hemorrhagic pulmonary edema associated with meat tenderizer treatment for esophageal meat impaction.

We describe a case of acute hemorrhagic pulmonary edema caused by aspiration of Adolph's meat tenderizer, used in an attempt to relieve an esophageal meat impaction. We performed an animal experiment in which bronchial instillation of a similar solution reproduced the clinical findings in our patient. This is a previously unreported and potentially lethal complication of a therapy that has never been submitted to clinical trials. We recommend against the use of this therapy for patients with complete esophageal obstruction or in those otherwise at risk for aspiration.

Pneumocystis hepatitis and choroiditis despite successful aerosolized pentamidine pulmonary prophylaxis.

A patient who developed Pneumocystis carinii hepatitis and choroiditis despite receiving prophylactic pentamidine therapy by aerosol is described. Liver biopsy showed histology typical of Pneumocystis hepatitis, but his respiratory status was stable and his lungs were free of P carinii organisms on BAL. Thus, inhaled pentamidine prophylaxis did not prevent extrapulmonary pneumocystosis. Patients receiving pentamidine prophylaxis with unexplained symptoms should undergo investigation for possible extrapulmonary P carinii infection.

Lung abscess caused by Legionella micdadei.

We describe a case of lung abscess caused by sporadic infection with Legionella micdadei in a patient with AIDS. L micdadei infection can be very difficult to diagnose because the organism stains only weakly Gram negative, requires special culture media, and is not detectable with some direct fluorescent antibody tests that are directed only at Legionella pneumophila. Since it can stain acid fast, it may be confused with mycobacteria. The abscess was successfully treated using antibiotics and percutaneous catheter drainage.

Effects of positive end-expiratory pressure on intracranial pressure in dogs with intracranial hypertension.

Positive end-expiratory pressure (PEEP) is used to improve oxygenation in patients with the adult respiratory distress syndrome. Nevertheless, this treatment may increase intracranial pressure (ICP) and be detrimental to certain neurosurgical patients. This clinical situation was simulated by administering PEEP to dogs with normal and elevated ICP. Increases in PEEP increased ICP in all animals. However, the presence of intracranial hypertension diminished the increase in ICP seen at a given level of PEEP. Cerebral perfusion pressure also fell less in the presence of intracranial hypertension than it did in the absence, although in the former situation cerebral perfusion pressure was at the lower limits of the range of cerebral autoregulation. These findings suggest that PEEP is no more detrimental to patients with elevated ICP than it is to patients whose ICP is normal, assuming that their cerebral autoregulation is not impaired.

Pulmonary complications from nasoenteral feeding tube insertion in an intensive care unit: incidence and prevention.

We prospectively evaluated 71 nasoenteral feeding tube insertions in critically ill patients and found a 4% incidence of pulmonary complications. All pulmonary complications occurred in tracheally intubated patients. To prevent these complications, we developed an enteral feeding tube insertion technique using a 26-Fr red rubber catheter as an introducer for a 8-Fr feeding tube. This technique is easy to perform by hospital staff and well tolerated by patients. No pulmonary complications occurred in 31 subsequent feeding tube insertions.

Miliary tuberculosis and adult respiratory distress syndrome.

Three patients with miliary tuberculosis developed the adult respiratory distress syndrome. In two patients this complication developed despite treatment with antituberculous drugs. The third patient developed the syndrome, but miliary tuberculosis was not suspected. The presence of disseminated intravascular coagulation in all three cases suggests a possible pathophysiologic relation. Miliary tuberculosis should be considered in patients presenting with adult respiratory distress syndrome of unknown cause.

Increasing intracranial pressure with air causes air embolism, not neurogenic pulmonary edema.

In an effort to duplicate a previous model of neurogenic pulmonary edema (NPE), we maintained intracranial pressure (PIC) at 20 Torr below mean arterial pressure in six closed-chested dogs anesthetized with alpha-chloralose and urethan. This was accomplished by infusing 1) isotonic saline (NS), 2) a gas mixture of 80% helium and 20% oxygen (HeO2), or 3) 100% carbon dioxide (CO2) through a trephined hole into the subdural space. Three more animals were studied with the same protocol after thoracotomy to permit Doppler examination for bubbles in the left pulmonary artery. Significant increases in pulmonary artery pressure, pulmonary vascular resistance, physiological shunt, dead space fraction, and hypoxemia were recorded when Pic was elevated by HeO2 infusion but not during infusion of NS or CO2. Pulmonary gas-bubble embolism was suggested by an increase in the fraction of helium in expired gas during HeO2 infusion and confirmed by Doppler recordings. We conclude that increasing Pic with air produces the physiological changes of air embolism; this is not a satisfactory model for investigating NPE.

Hyperthyroidism induced by iodinated glycerol.

We report a case of iodide-induced thyrotoxicosis after the use of iodinated glycerol (Organidin) for the symptomatic treatment of chronic obstructive pulmonary disease. In patients with severe chronic obstructive pulmonary disease, symptoms of hyperthyroidism may be overlooked. Hyperthyroidism may be induced by any iodinated expectorant, especially in patients with preexisting thyroid disease.

Suppurative Candida phlebitis of a peripheral vein.

A patient receiving total parenteral alimentation through a central catheter developed fatal candida sepsis originating from suppurative phlebitis of a peripheral vein. This case underscores the importance of aggressively pursuing all potential endovascular sources of fungemia in susceptible patients: those on antibiotics, with chemical phlebitis, and hyperglycemia.

Effect of positive end-expiratory pressure on intracranial pressure in dogs.

Application of positive end-expiratory pressure to dogs with noncardiogenic pulmonary edema increased intracranial pressure (measured as cerebrospinal fluid pressure) and decreased cerebral perfusion pressure. The magnitude of these changes depended on the amount of end-expiratory pressure applied and the lung compliance.

Pulmonary arteriovenous fistulas: increase in shunt at high lung volume.

Intrapulmonary shunt measured in the sitting position by the oxygen breathing method increased at total lung capacity in 7 of 8 patients with pulmonary arteriovenous fistulas. This may explain the clinically noted increased murmur over a fistula on inspiration. The finding of an increased intrapulmonary shunt at total lung capacity might suggest the diagnosis in equivocal cases and provide a convenient test for follow-up after surgery.

Mechanism by which positive end-expiratory pressure increases cerebrospinal fluid pressure in dogs.

We investigated possible mechanisms by which positive end-expiratory pressure (PEEP) increased cerebrospinal fluid pressure (PCSF) in anesthetized mechanically ventilated dogs. In part I of the study, PEEP was applied in 5 cmH2O increments each lasting 1-2 min, before and after a snare separated the spinal from the cerebral subarachnoid space in each animal. Next, with the spinal cord still ligated, the dogs were ventilated without PEEP while superior vena cava pressure (PSVC) was raised in 5 cmH2O increments by means of a fluid reservoir connected with the superior vena cava. Cerebrospinal fluid pressure in the cisterna magna increased immediately and in parallel with PEEP before and after the spinal subarachnoid space was occluded and also increased when PSVC was raised independently; in all circumstances the increase in PCSF correlated closely with PSVC (r = 0.926). In part II of the study, arterial blood gases were drawn before and after PEEP was applied in the same increments and for the same duration as in part I. Cerebrospinal fluid pressure measured with a hollow skull screw again rose in parallel with PEEP, whereas arterial carbon dioxide tension rose only slightly at 60 s. In part III of the study, mean arterial pressure (Pa) was allowed to decrease with PEEP or was held constant by distal aortic obstruction and volume infusion. Cerebrospinal fluid pressure increased regardless of Pa, but the increase was greater when Pa was held constant than when it fell with PEEP. We conclude that PEEP increases PCSF primarily by increasing PSVC and decreasing cerebral venous outflow. This effect is augmented if cerebral arterial inflow is increased as well.

Respiratory distress syndrome from lymphangiography contrast medium.

Adult respiratory distress syndrome (ARDS) has been reported as a rare complication of lymphangiography with ethiodized oil. We report 2 patients who developed otherwise unexplained pulmonary edema after lymphangiography, and describe an animal model of pulmonary injury after an injection of ethiodized oil. We injected 0.25 ml/kg of body weight intravenously into 45 rabbits, and followed arterial blood gases and/or killed the rabbits randomly at various intervals for morphologic lung examination by light and electron microscopy. Within 24 h after injection, there was moderate hypoxemia from oil embolization, but only minimal lung edema. However, by 2 to 4 days after injections, hypoxemia was most severe and was accompanied by extensive alveolar and interstitial inflammation, hemorrhage, and edema. After 4 days, there was gradual blood gas and morphologic recovery, with complete restoration of normal anatomy by 6 wk. Our data showed that in rabbits, ethiodized oil can reproducibly cause delayed, severe pulmonary injury, thus supporting the clinical reports that ARDS may occur several days after lymphangiography.

A Starling resistor regulates cerebral venous outflow in dogs.

This investigation was undertaken to determine whether a Starling resistor or venous waterfall effect exists between the sagittal sinus and the cerebral veins such that increases in sagittal sinus pressure (Pss) do not abolish cerebral venous outflow and to examine two possible contributions of extracranial venous valves in regulating outflow. Anesthetized dogs were subjected to positive end-expiratory pressure (PEEP) before and after intracranial pressure (Pic) was elevated by inflation of an epidural balloon. PEEP raised Pss equally in all animals, but Pic and cerebral venous pressure (Pcv) increased less in the presence of intracranial hypertension. When Pss was low, passage of a catheter in the cerebral vein in and out of the sagittal sinus demonstrated an abrupt drop in pressure as the sinus was entered. When Pss was raised and lowered independently of superior vena caval pressure (Psvc) the changes in Pic and Pcv were less when Pss was decreased than when it was increased. Sustained increases and decreases in Psvc caused increases and decreases in Pcv, Pic, Pss, and external jugular venous pressure (Pejv) regardless of whether external jugular venous valves were present or absent. We conclude that a Starling resistor between the sagittal sinus and the cerebral veins regulates cerebral venous outflow when Pss is increased by PEEP and other maneuvers that raise Psvc. The waterfall maintains Pcv and Pic at normal levels when Psvc and Pss are reduced. Extracranial venous valves are not essential to this mechanism.

Influence of head-dependent positions on lung volume and oxygen saturation in chronic air-flow obstruction.

We investigated the influence of head-dependent positions upon functional residual capacity (FRC) and arterial oxygen saturation in 25 patients with clinically stable chronic air-flow obstruction and 25 normal subjects. Lung volume was measured by gas dilution in normal subjects and by plethysmography in patients with chronic obstructive pulmonary disease (COPD). Arterial oxygen saturation was determined by ear oximetry. In normal subjects, sitting FRC declined by 29.9% when a horizontal-supine posture was assumed, but underwent little further change as the supine subject was tilted head-downward to -25 degrees. Lateral decubitus positions caused declines from sitting FRC of 17.1% at 0 degrees, and 27.4% at -25 degrees. In contrast, patients with COPD experienced negligible changes in lung volume as position was varied. The mean falls from sitting FRC were 3.5% and 1.9% in the 0 degree supine and 0 degree lateral decubitus postures, respectively, and little further volume loss occurred in head-dependency. Eight patients actually increased FRC when recumbent. Positional lung volume changes measured by gas dilution exceeded those measured by plethysmography, suggesting that increased air trapping helped to maintain FRC as position was altered. Patients with COPD did not desaturate in any position tested. We conclude that patients with advanced COPD conserve lung volume and do not desaturate when tipped into head-dependent positions. Reduction of FRC is unlikely to contribute to the hypoxemia or dyspnea previously reported to occur in these patients during chest physiotherapy.

The role of transbronchial biopsy for the diagnosis of diffuse pneumonias in immunocompromised marrow transplant recipients.

We studied the use of transbronchial biopsy for the diagnosis of diffuse pneumonia in marrow transplant recipients. Transbronchial biopsy results were directly compared with open-lung biopsy results by performing the procedures simultaneously in the same lobe of the lung and processing the specimens in parallel. There were 24 cases of pneumonia diagnosed in 22 patients. Transbronchial biopsy correctly identified 3 of 5 cases of Pneumocystis carinii and none of the 5 cases of viral pneumonia. The overall sensitivity of transbronchial biopsy was 58%, with a 13% incidence of moderate hemorrhage and no deaths. We conclude that the open-lung biopsy remains the procedure of choice for the diagnosis of acute, diffuse pneumonia in the immunocompromised marrow transplant recipient.