A randomized, prospective evaluation of noninvasive ventilation for acute respiratory failure.

We compared noninvasive positive-pressure ventilation (NPPV), using bilevel positive airway pressure, with usual medical care (UMC) in the therapy of patients with acute respiratory failure (ARF) in a prospective, randomized trial. Patients were subgrouped according to the disease leading to ARF (chronic obstructive pulmonary disease [COPD], a non-COPD-related pulmonary process, neuromuscular disease, and status postextubation), and were then randomized to NPPV or UMC. Thirty-two patients were evaluated in the NPPV group and 29 in the UMC group. The rate of endotracheal intubation (ETI) was significantly lower in the NPPV than in the UMC group (6.38 intubations versus 21.25 intubations per 100 ICU days, p = 0.002). Mortality rates in the intensive care unit (ICU) were similar for the two treatment groups (2.39 deaths versus 4.27 deaths per 100 ICU days, p = 0.21, NPPV versus UMC, respectively). Patients with hypoxemic ARF in the NPPV group had a significantly lower ETI rate than those in the UMC group (7.46 intubations versus 22.64 intubations per 100 ICU days, p = 0.026); a similar trend was noted for patients with hypercapnic ARF (5.41 intubations versus 18.52 intubations per 100 ICU days, p = 0.064, NPPV versus UMC, respectively). Patients with ARF in the non-COPD category had a lower rate of ETI with NPPV than with UMC (8.45 intubations versus 30.30 intubations per 100 ICU days, p = 0.01). Although the rate of ETI was lower among COPD patients receiving NPPV, this trend did not reach statistical significance (5.26 intubations versus 15.63 intubations per 100 ICU days, p = 0.12, NPPV versus UMC, respectively). In conclusion, NPPV with bilevel positive airway pressure reduces the rate of ETI in patients with ARF of various etiologies.

Split-night studies for the diagnosis and treatment of sleep-disordered breathing.

We examined the effect of split-night polysomnography on compliance with positive pressure via a mask for the treatment of obstructive sleep-disordered breathing. A comparison of objective compliance (hours/day) at the first meter read from the positive-pressure device (4-6 weeks after set-up) in patients who had a successful split-night positive-pressure titration vs. patients who had traditional full-night positive-pressure titration was performed. Patients were matched for age, sex, and severity of the obstructive sleep-disordered breathing. Twelve patients were matched with controls who underwent full-night polysomnography. There were no significant differences between the split-night patients and the full-night patients with regard to age, sex, body mass index, and pretreatment Epworth Sleepiness Score. In addition, there was no significant difference between apnea-hypopnea index and the desaturation-event frequency for both groups pre- and post-treatment. The average daily use of continuous positive airway pressure (CPAP) at the time of the first meter reading in the group that underwent full-night positive-pressure titrations as opposed to split-night titrations was 5.2 hours/day +/- 2.2 vs. 3.8 hours/day +/- 2.9, respectively (p = 0.29). The Epworth Sleepiness Scale on the initial clinic visit (as an index of patient-perceived impairment) did not predict compliance at 4-6 weeks. The time at the final positive pressure did not correlate with compliance. Acceptance of positive pressure in the split-night patients ranged from 62 to 67%.

Resolution of obstructive sleep apnea after microvascular brainstem decompression.

Lesions of the brainstem have been associated with obstructive sleep apnea in previous reports. We now report a case in which retromastoid craniectomy with microvascular decompression of the medulla and ninth and tenth cranial nerves resulted in the complete resolution of severe obstructive sleep apnea. Possible mechanisms for this observation are discussed.

CPAP therapy via oronasal mask for obstructive sleep apnea.

STUDY OBJECTIVE: To determine the effectiveness of oronasal masks for positive pressure therapy in alleviating obstructive sleep apnea (OSA). METHODS AND PROCEDURES: Polysomnographic records of all 245 patients with OSA who underwent therapeutic trials of either continuous positive airway pressure (CPAP) or bilevel positive airway pressure between January 1991 and December 1992 were reviewed. Thirty patients who had been prescribed positive pressure therapy employing an oronasal mask were identified. Two patients known to be successfully treated with CPAP via oronasal mask underwent repeat polysomnography. The initial portion of the study was a diagnostic evaluation during which the patients were untreated. During the second portion of the study, both patients used CPAP via an oronasal mask while wearing a mouthpiece designed to maintain oral patency. RESULTS: The 30 patients with OSA who were identified in this study had significant amelioration of OSA while receiving positive pressure therapy via oronasal mask compared with the baseline, diagnostic polysomnogram (apnea index: 55.3 +/- 36.9-->1.6 +/- 3.7, p < 0.001; hypopnea index: 21.2 +/- 20-->2.7 +/- 4.9, p < 0.001; nadir of SaO2: 72.5 +/- 13.9-->87.1 +/- 4.3, p < 0.001, mean +/- SD). Improvement of OSA did not depend on maintenance of a closed mouth, as evidenced by elimination of sleep-disordered breathing in the two patients receiving positive pressure via oronasal mask while wearing a mouthpiece to keep the mouth open. CONCLUSION: Oronasal masks are a viable alternative interface for alleviating OSA with positive pressure therapy in those patients who are unwilling or unable to tolerate conventional nasal interfaces. Although there were no adverse consequences associated with the use of oronasal masks in our patients, appropriate safety precautions should be taken to minimize the possibility of aspiration of gastric contents and avoid untoward sequelae due to positive pressure device failure.

Accuracy of end-tidal and transcutaneous PCO2 monitoring during sleep.

STUDY OBJECTIVE: Although it is intuitively desirable, the measurement of arterial carbon dioxide tension (PaCO2) during diagnostic polysomnography and nocturnal trials of positive pressure therapy is invasive and potentially expensive. The accuracy of end-tidal carbon dioxide tension (PETCO2) and transcutaneous carbon dioxide (tcPCO2) monitoring in these contexts has not been systematically evaluated. This investigation was undertaken to evaluate the accuracy of PETCO2 and tcPCO2 in patients undergoing polysomnography. METHODS AND PROCEDURES: Values of PETCO2 were compared with PaCO2 in 19 patients spontaneously breathing room air (condition 1), in 13 patients receiving supplemental oxygen via nasal cannula (condition 2), and in 22 patients receiving nocturnal positive pressure ventilatory assistance (all but one with continuous positive airway pressure or bilevel positive airway pressure) (condition 3). The accuracy of tcPCO2 monitoring during sleep was also examined by comparing tcPCO2 values with simultaneously recorded PaCO2 values obtained during sleep in patients undergoing nocturnal polysomnography. Data were collected using three commercially available brands of tcPCO2 monitors (capnograph R, n = 17 patients; capnograph S, n = 17; and capnograph N, n = 15). RESULTS: Accuracy of PETCO2--There was significant scatter in the PaCO2 vs PETCO2 relationship such that only 23 percent of the variability in PaCO2 was explained by variation of PETCO2 during condition 1 and only 15 percent and 20 percent of the variability in PaCO2 was explained by variation of PETCO2 during conditions 2 and 3, respectively. 21.3 percent of patients had average PETCO2 values in error by > 10 mm Hg during condition 1, while during conditions 2 and 3, 46.2 and 63.7 percent of patients had average values in error by > 10 mm Hg, respectively. Accuracy of tcPCO2--While capnographs S and N generally overestimated PaCO2 with a wide scatter, capnograph R tended to have offsetting overestimations and underestimations of PaCO2 with a wide scatter. With each capnograph, a relatively small portion of the variability of the PaCO2 was explained by variability of the tcPCO2 (r2 = 0.2, 0.45 and 0.64 for capnographs S, N, and R, respectively). Across the three capnographs, 43.1 to 66.7 percent of measurements were in error by > 10 mm Hg, and 5 to 20 percent of measurements reflected errors > 20 mm Hg. There was no consistent relationship between the tcPCO2 error and the level of PaCO2, nor was the tcPCO2 error consistent in individual patients. There was no relationship between tcPCO2 accuracy and body mass index. CONCLUSION: Neither PETCO2, measured within a face mask, nor tcPCO2 is a consistently accurate reflection of PaCO2. This limits the utility of these variables in monitoring patients during diagnostic and therapeutic sleep studies, and in particular, during trials of nocturnal ventilatory assistance where adequate levels of support are to be established and unacceptable hyperventilation and respiratory alkalosis must be recognized.

Adequacy of prescribing positive airway pressure therapy by mask for sleep apnea on the basis of a partial-night trial.

We tested the hypothesis that a prescription for positive-pressure therapy (including pressure level, patient-device interface, and positive-pressure modality, e.g., CPAP or BiPAP) for obstructive sleep apnea (OSA) can be developed on the same night as the polysomnographic (PSG) diagnosis is made. Fifty consecutive patients with OSA in whom a partial-night PSG diagnosis was made (PSGD) underwent a therapeutic trial of positive-pressure therapy during the remainder of the night (PSG-PPP). The average apnea index during PSGD was 54.96 +/- 36.3 (mean +/- SD). On a subsequent full-night PSG (PSG-PPF), the prescription was tested. Thirty-one of the 50 patients were satisfactorily treated with CPAP, without variation of the interface during both PSG-PPP and PSG-PPF. In these patients the average pressure prescription while receiving PSG-PPF was statistically higher than during PSG-PPP (11.77 +/- 3.6 versus 10.56 +/- 3.6 cm H2O, respectively, p = 0.002). In 14 of these 31 patients (45%) some alteration in pressure requirement was necessary during PSG-PPF. Eleven patients required 2.5 cm H2O higher pressure and three patients required 5 cm H2O higher pressure during PSG-PPF than during PSG-PPP. There was a change of interface across the two therapeutic trials in 15 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Verapamil overdose: case report and review of the literature.

OBJECTIVE: To report the presentation and controversies regarding therapy of an 18-year-old man following a life-threatening ingestion of verapamil. CASE SUMMARY: An 18-year-old man ingested large quantities of dipyridamole, trimethoprim/sulfamethoxazole, amoxicillin, and verapamil. He presented to an outlying hospital and was initially conscious. Soon thereafter, the patient had a seizure; he required intubation, developed cardiac conduction abnormalities, and became hypotensive. The patient required pharmacologic pressors and a pacemaker for transfer to our institution. At our institution, vigorous fluid resuscitation, cardiac pacing, and careful attention to acid/base and electrolyte management provided the basis of therapy. The patient recovered without deficit and was discharged from the intensive care unit five days later. DISCUSSION: Current controversies regarding the management of verapamil overdose are reviewed. Removal of the drug by gastric lavage is a mainstay of therapy. Administration of syrup of ipecac is contraindicated. Although specific recommendations for calcium dosing in the overdose situation have not been rigorously studied, maintenance of a normal serum ionized calcium concentration is suggested. An exogenous catecholamine, rather than dopamine, may be the drug of choice for treating hypotension. Cardiopulmonary bypass provides a method for drug removal in cases of severe toxicity; however, this invasive method requires further study. Management of fluid/electrolyte, acid/base, and ventilation abnormalities is required to treat large ingestions of verapamil. Treatment guidelines for critical care clinicians are provided.

Subclinical pneumonitis due to Pneumocystis carinii in a young adult with elevated antibody titers to Epstein-Barr virus.

Pneumocystis carinii was recovered from the lungs of a 20-year-old woman in apparent good health who had volunteered to undergo bronchoalveolar lavage (BAL) as a normal control subject. Total and differential cell counts in the BAL fluid revealed a significantly increased number and proportion of T lymphocytes, although the CD4:CD8 ratio was in the normal range. Despite the lack of specific antibiotic therapy, in a subsequent lavage no P. carinii were recovered, and the total and differential cell counts returned to normal, suggesting that the infection had resolved. Serologic evaluation revealed no evidence of human immunodeficiency virus infection, although elevated titers of antibodies to Epstein-Barr virus were demonstrated, suggesting ongoing or resolving viral infection. These findings suggest that P. carinii may cause subclinical pneumonitis even in the absence of a clinically evident immune deficient state. Furthermore, an increase in cell count and in the proportion of lymphocytes in an otherwise unremarkable BAL may indicate the presence of P. carinii in the airways and may be the only sign of subclinical infection of the respiratory tract by this organism.

Endothelial cells inhibit receptor-mediated superoxide anion production by human polymorphonuclear leukocytes via a soluble inhibitor.

Confluent monolayers of bovine pulmonary artery endothelial cells (BPAE) or human umbilical vein endothelial cells (HUVE) inhibited by 80 to 90% the production of O2- by added human neutrophils (PMNs) stimulated by plasma membrane receptor-mediated activators (formylmethionylleucylphenylalanine [fMLP], opsonized zymosan, heat-killed Staphylococci), but not by non-plasma membrane receptor-mediated activators (phorbol myristate acetate and delta-hexachlorocyclohexane). Degranulation induced by fMLP was also inhibited by BPAE. Inhibition was not affected by eicosatetraynoic acid (ETYA) or indomethacin. To assess the role of cell-cell contact, 0.45-microns-pore culture plate inserts were employed to prevent PMN-endothelial cell contact during incubation. A similar amount of inhibition of stimulated PMNs superoxide production was seen as compared to PMN-endothelial incubations where contact occurred. A soluble component released by BPAE monolayers, when added to PMNs, duplicated the inhibition seen by BPAE-PMN co-incubation. Incubation of BPAE with adenosine deaminase did not reduce inhibition of O2- production compared to controls without adenosine deaminase. There was no evidence of endothelial scavenging of O2- generated by hypoxanthine-xanthine oxidase, and inhibition of endothelial superoxide dismutase did not diminish the inhibitory effort. We conclude that cell contact is not required for BPAE inhibition of fMLP-stimulated O2- production by PMN, and that scavenging of superoxide anion is not the mechanism. The inhibitor appears to be a polypeptide with an apparent molecular weight between 1,000 and 10,000 D and does not appear to be adenosine, an arachidonate metabolite, or superoxide dismutase. The mechanism may involve down-regulation of plasma membrane receptor-mediated activation of PMNs.

Immunosuppression by spleen cells from Moloney leukemia. III. Evidence for a suppressor cell that is not the leukemic, virus-producing cell.

Spleens of mice bearing MuLV (Moloney)-induced leukemia contain cells that inhibit the antibody response of normal syngeneic lymphocytes to sheep RBC in Marbrook cultures. In order to determine whether these immunosuppressive cells are virus-infected tumor cells or normal cells we pretreated leukemic spleen cell suspensions with syngeneic mouse antiserum to Moloney leukemia antigen(s) (plus complement) and with rat anti-Moloney serum (plus complement). The cytotoxic treatment killed approximately 20% to 30% and 60% to 70% of the cells, respectively. The remaining viable cell population was tested for MuLV production (in an infectious center assay on S+L-fibroblasts), for lethal effect on newborn mice, and for immunosuppressive activity. After the treatment with anti-Moloney sera the number of MuLV-releasing cells decreased 10-fold and the leukemogenic potential in vivo decreased 100-fold as compared to leukemic spleen cells pretreated with nonimmune mouse and rat sera (plus complement). In contrast, the ability of the antisera-treated cells to inhibit anti-SRBC response remained undiminished. This indicates that, in part, the immunosuppressive cells in the leukemic spleen are normal, noninfected cells, involved, perhaps, in immune regulation.

Immunosuppression by spleen cells from Moloney leukemia. Comparison of the suppressive effect on antibody response and on mitogen-induced response.

The inhibitory effect of cells from leukemic spleens on the immune functions of normal lymphocytes was studied. Suppressor cells were obtained as the nonadherent fraction (NA) from splenic tumors of mice infected with MuLV-Moloney. This fraction (NA MuLV- M) contained less than 10% membrane Ig-positive (Ig+) cells, 45 to 60% theta-positive cells (theta+) and 40 to 50% naught cells (theta-, Ig-). Similarly prepared fractions from normal control spleens (NAc) containing 75 to 90% theta+cells and less than 10% Ig+ and naught cells were utilized in control cultures. Addition of the NA MuLV- M cells into cultures (Marbrook system) of normal spleen cells with sheep red blood cells suppressed the specific antibody response determined by the number of hemolytic plaque forming cells (PFC). The PFC response was significantly suppressed at a suppressor cell to responder cell ratio of 1:100, and was completely abolished at a ratio of 1:10 or higher. The control NAc fraction showed some inhibitory effect only at high suppressor to responder ratios (1:2 or 1:1). In contrast, the suppressive effect of NAMuLV-M on mitogen-induced 3H-thymidine incorporation in normal B and T cells was much weaker. Very little, if any, suppression occurred at the ratio of 1:100 or 1:10, however, about 50% decrease in DNA synthesis was observed at the ratio 1:2 or 1:1. On the basis of this differential suppressive effect, it is suggested that leukemic spleen cells can suppress the function of immunocompetent cells by more than one mechanism.

Aggregation and release in thrombocytes of the duck.

Avian thromboyctes are aggregated by a number of substances that cause platelet aggregation, and evidence suggests that this response is related to the release of serotonin (5-hydroxytryptamine, 5-HT) from intracellular granules. In this study duck thrombocytes released 5-HT during collagen-induced aggregation, but thrombocytes incubated with 14C-labeled adenine did not release radioactive adenine nucleotides. These results indicate the existence of a metabolic pool of adenine nucleotides that is separate from released constituents of the cell. No unlabeled adenine compounds were detected in the supernatants of aggregated thrombocytes indicating either the rapid alteration of released nucleotides or the absence of a specific release pool of adenine nucleotides. Finally there is no release of the intracellular enzyme markers, lactate dehydrogenase, beta-glucuronidase, and acid phosphatase, during collagen-induced aggregation. These findings suggest that avian thrombocytes exhibit a specific release reaction and that serotonin acts as the functional counterpart of ADP in platelet aggregation.