Rapid alveolar epithelial fluid clearance following lung lavage in pulmonary alveolar proteinosis.

STUDY OBJECTIVE: To measure the in vivo rate of alveolar epithelial fluid clearance of the human lung in patients with pulmonary alveolar phospholipoproteinosis (PAP). DESIGN: Prospective clinical study. SETTING: The medical-surgical ICUs of a university teaching hospital. PATIENTS: Four patients with idiopathic PAP requiring therapeutic lung lavage. INTERVENTIONS: Large-volume lung lavage with isotonic saline solution using fiberoptic bronchoscopy followed by serial sampling of alveolar fluid using a wedged bronchial catheter. MEASUREMENTS AND RESULTS: The rate of alveolar epithelial fluid clearance was calculated by measuring the concentration of protein in sequential samples. Alveolar epithelial fluid clearance over the first hour after lung lavage was 53 +/- 14% (mean +/- SD). Sequential samples in two patients indicated a sustained high rate of clearance over several hours. Plasma and alveolar fluid epinephrine levels were in the normal range in two patients. CONCLUSIONS AND SIGNIFICANCE: Alveolar fluid clearance is rapid after lung lavage in patients with PAP and appears to be driven by catecholamine-independent mechanisms. The rapid rate of alveolar epithelial fluid transport explains why patients with PAP tolerate large-volume lung lavage.

A comparison of 2 methods of measuring rectal temperatures with digital thermometers.

BACKGROUND: Digital rectal thermometers typically have 2 distinct modes of operation: dwell or monitor, in which body temperature is displayed continuously, and predictive, in which body temperature is mathematically estimated on the basis of the curve of temperature rise that occurs after the thermometer is inserted. Although the dwell mode is generally considered more accurate, the predictive mode allows more rapid measurement. Direct comparisons of these 2 methods are lacking. OBJECTIVE: To determine if measurements of rectal temperatures obtained with the predictive mode differ significantly from those obtained with the dwell mode. METHODS: For each of 10 subjects, both dwell and predictive modes were used to measure early morning rectal temperature. For comparison of the 2 modes during states of temperature flux, 8 subjects had rectal temperatures measured after swimming in cold water. Initial predictive values were measured directly after each subject exited from the water. Initial dwell values were estimated by linear extrapolation of measured 3- and 6-minute dwell values. Paired-sample statistical methods were used to compare data. RESULTS: Measurements of early-morning temperatures obtained with the predictive mode did not differ significantly from those obtained with the dwell mode (P = .64). Predictive values also did not differ significantly from extrapolated dwell values for measurements obtained during mild temperature flux after immersion in cold water (P = .33). CONCLUSION: The predictive and dwell modes of digital rectal thermometers yield similar measurements of temperature during steady-state conditions and during states of mild temperature flux.

Hypothermia and afterdrop following open water swimming: the Alcatraz/San Francisco Swim Study.

To determine whether or not participants in open water swim events experience hypothermia and afterdrop, rectal temperature was measured for up to 45 minutes in 11 subjects following the New Year's Day Alcatraz Swim. This event was held in open water (11.7 degrees C [53.0 degrees F]) in the San Francisco Bay, and participants did not wear wetsuits or other protective clothing. Biophysical parameters, including surfacelvolume ratio, body mass index, and percent body fat were measured before the swim, and statistical analysis was done to determine predictors of temperature decrease and afterdrop duration. Applying the American Heart Association definition of hypothermia (less than 36.0 C [96.8 degrees F]), hypothermia was seen in 5 of the 11 subjects. Using a more rigorous and traditional definition (less than 35.0 degrees C [95.0 degrees F]), hypothermia was seen in only one subject. Afterdrop, defined as continued cooling following removal from cold stress, was seen in 10 of the 11 subjects. Surface/volume ratio (S/V) and body mass index (BMI) predicted the lowest recorded temperatures (P < .05; r(S/V) = -.71, r(BMI) = .72) and afterdrop duration (P < .05; r(SN) = -.75, r(BMI) = .69). These results suggest that hypothermia and afterdrop can occur commonly after recreational open water swimming, and that participants should be observed for signs of temperature decrease following removal from cold stress.

Short-term potentiation of ventilation after different levels of hypoxia.

Short-term potentiation of ventilation (VSTP) may be observed in healthy subjects on sudden termination of an hypoxic stimulus. We hypothesized that the level of hypoxia preceding normoxia would modify the duration and magnitude of the ensuing ventilatory decay. Ten healthy adults were studied on two different occasions, during which they were randomly exposed to isocapnic 6 or 10% O2 for 60 s and then switched to an isocapnic normoxic gas mixture. Both hypoxic gases induced significant ventilatory responses, and mean peak minute ventilation before the isocapnic normoxic switch was higher in 6% O2 (P < 0.001). The fast time constant of the two-exponential equation representing the best fit for ventilatory decay was unaffected by the magnitude of the hypoxic stimulus. However, the slow time constant, which is considered to represent VSTP, was markedly prolonged in 6% compared with 10% O2 [106.7 +/- 11.3 vs. 38. 2 +/- 6.1 (SD) s, respectively; P < 0.0001]. This result indicates that VSTP is stimulus dependent. We conclude that the magnitude of hypoxia preceding a normoxic transient modifies VSTP characteristics. We speculate that the interdependence function of ventilatory stimulus and short-term potentiation is crucial for preservation of system stability during transitions from high to low ventilatory drives.

Nitric oxide modulates anoxia-induced gasping in the developing rat.

Gasping is an important mechanism for survival. Nitric oxide (NO) plays an excitatory role in brainstem regions mediating respiratory responses to hypoxia. We hypothesized that neural structures mediating anoxia-induced gasping would display NO dependency. Two- to 15-day-old rat pups underwent anoxic exposures with 100% N2 in a plethysmograph following administration of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) blocker, L-arginine (L-Arg), a NO precursor, or normal saline. In general, gasp latencies were significantly shorter after L-Arg, and were prolonged with L-NAME. Furthermore, NOS inhibition prolonged gasping duration and reduced gasping frequency at all postnatal ages, although this effect was particularly increased with advancing postnatal age. NADPH-diaphorase staining and Western blots of protein lysates from the lateral tegmental field, the putative neural center underlying gasp generation, revealed progressively increased neuronal NOS abundance with animal maturation. We conclude that anoxia-induced gasping neurogenesis is modulated by NO mechanisms in neonatal pups. We postulate that higher NO brainstem concentrations may favor early autoresuscitation but be detrimental to overall survival during prolonged asphyxia.

Nitric oxide modulates ventilatory responses to hypoxia in the developing rat.

Nitric oxide (NO) is an important excitatory neurotransmitter in the central nervous system. In the adult rat, both selective and nonselective blockers of constitutive nitric oxide synthase (NOS) induce marked ventilatory reductions during sustained hypoxia, thereby enhancing ventilatory roll-off. Since hypoxic ventilatory depression is greater in developing mammals during the late phases of hypoxic exposure, we hypothesized that limited NOS activity may play a role in the late arm of the ventilatory response. To test our hypothesis, 5-d-, 10-d-, and 15-d-old rat pups underwent a 30-min hypoxic challenge (10% O2) before and after administration of 100 mg/kg N-nitro-L-arginine methyl ester (L-NAME), a competitive NOS inhibitor. Minute ventilation (VE) was measured using whole-body plethysmography. In 5-d-old pups, early VE hypoxic responses were enhanced, and late VE were similar after administration of L-NAME. In contrast, in 15-d-old hypoxic pups, L-NAME administration was associated with smaller early VE increments and significantly larger VE reductions when compared with pretreatment conditions. The role of central nervous system NO in the development of these ventilatory changes was further assessed by Western blots of protein equivalents from the nucleus tractus solitarius (NTS), the first central relay for peripheral chemoreceptor afferent input, which revealed increasing neuronal NOS expression with age. Furthermore, NADPH-diaphorase immunohistochemical staining of neurons in the NTS revealed increased positively labeled neuronal populations within subnuclei of this structure with advancing postnatal age. Current findings suggest that NOS activity mediates both excitatory and inhibitory components of the hypoxic ventilatory response. Furthermore, in brainstem respiratory regions, NO may play a role in modulating the prominent second phase of the biphasic response to hypoxia typically seen in early postnatal life.

Heterozygous alpha 1-antitrypsin deficiency (PiSZ) in an adolescent with asthma.

Although alpha 1-antitrypsin deficiency has been associated with obstructive lung disease in individuals possessing a homozygous phenotype (PiZZ), this association has not been as clearly documented in heterozygous individuals (PiMZ, PiMS, and PiSZ phenotypes). Information regarding the heterozygous adolescent population is particularly lacking, making the evaluation and treatment of such patients difficult. We present the case of an adolescent with a history of asthma and heterozygous (PiSZ) alpha 1-antitrypsin deficiency and outline our management with reference to appropriate literature.

Characterization and developmental aspects of anoxia-induced gasping in the rat.

With increasing postnatal age, mammals display diminished tolerances for prolonged exposures to severe oxygen deprivation. Similarly, duration and efficiency of gasping, a unique mechanism for enhancing survival after anoxia-induced apnea, are also affected by postnatal age. We hypothesized that maturational patterns of anoxia-induced gasping may encompass more than a single monophasic phenomenon. Each of the putative phases of the gasping response may underlie unique characteristics which could be of relevance to survival capability. To study these issues, adult rats and rat pups at 2-3, 5, 10, 15, and 25 days of age underwent anoxic exposures with 100% N2 in a barometric chamber. In pups aged < 25 days but not thereafter, following an age-dependent period of central apnea, an initial gasping phase characterized by vigorous and frequent periodic bursts of a large inspiratory effort preceded and followed by expiration excursions emerged (phase I). This phase was followed by a period of relative respiratory silence of variable duration with occasional, interspersed phase I-like gasps (phase II). Finally, a third phase easily recognized by the onset of frequent inspiratory-only gasping efforts developed (phase III). The amplitude of phase III inspiratory gasps progressively diminished until their complete cessation. Although overlap between gasping phases was present, a marked age dependency in both duration and gasping frequency within each phase occurred. We conclude that anoxia-induced gasping responses in rat pups < 25 days old are triphasic in nature, exhibit defined phase-locked periodicities and respiratory effort patterns, and undergo significant maturation.

Age as a factor in critical care unit admissions.

BACKGROUND: Although the aged occupy a high proportion of critical care beds nationwide, few multicenter studies have been undertaken to specifically determine physician attitudes toward the elderly in a critical care setting. We attempt to determine the importance of patient age as a factor in the admission of acutely ill medical patients to critical care units. METHODS: In response to a hypothetical case scenario, physicians were asked to admit one of two patients to a last available critical care unit bed. An accompanying questionnaire was used to gain a ranking of several admission factors as compared with age, and to gain demographic data regarding the study population. Data were subjected to nonparametric statistical analysis. RESULTS: When age was the only difference between two patients in a hypothetical case scenario, 80.7% of respondents chose the younger patient (age 56 years) for admission, 13.2% chose the older patient (age 82 years), and 6.2% abstained. Following the provision of more detailed medical and social information, however, only 53.5% chose the younger patient, 41.2% chose the older patient, and 5.3% continued to abstain. In a ranking of several admission factors, age was found to be of less importance than severity of presenting illness, previous medical history, and do not resuscitate status, but of more importance than patient motivation, ability to contribute to society, family support, and ability to pay for care. When asked if they supported a definitive age criterion that would restrict all patients over a certain age from access to critical care units, 95.1% responded that they did not. CONCLUSIONS: Age is a factor considered by physicians in the admission of acutely ill medical patients to critical care units. Other medical and social factors, however, can affect the impact of patient age on treatment decisions. Further study and discussion are needed to clarify the appropriate role of age and other factors in critical care unit admissions.