David J. Pierson

Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome☆

Most patients with extreme obesity do not exhibit alveolar hypoventilation, but an intriguing minority do. The mechanism(s) of this phenomenon remain unknown. A disorder in ventilatory control has been suggested as a major factor in the pathogenesis of the obesity-hypoventilation syndrome. Accordingly, hypoxic and hypercapnic ventilatory drives were measured in 10 patients with the typical symptoms of the syndrome: obesity, hypersomnolence, hypercapnia, hypoxemia, polycythemia and cor pulmonale. Hypoxic ventilatory drive, measured as the shape parameter A, averaged 21.9 +/- 5.35, approximately one-sixth that in normal controls, A = 126 +/- 8.6 (P less than 0.01). The ventilatory response to hypercapnia also was markedly reduced, the slope of the response averaging 0.51 +/- 0.005, or about one-third the normal value of 1.83 +/- 0.13 (P less than 0.01). This decreased responsiveness in hypoxic and hypercapnic ventilatory drive was consistent throughout the group. The depression in ventilatory drive found in the obesity-hypoventilation syndrome may be causally related to the alveolar hypoventilation manifested by these patients.

TESTOSTERONE REPLACEMENT IN HYPOGONADAL MEN: EFFECTS ON OBSTRUCTIVE SLEEP APNOEA, RESPIRATORY DRIVES, AND SLEEP

The obstructive sleep apnoea syndrome occurs predominantly in men. To determine the effect of testosterone on ventilatory function and whether testosterone may play a role in the development of obstructive apnoea, we performed waking ventilatory drive studies and sleep studies in five hypogonadal men. These androgen‐deficient subjects were studied both while receiving no treatment and after six weeks of testosterone replacement therapy (testosterone oenanthate 200 mg i.m. every 2 weeks). Hypoxic ventilatory drive decreased significantly, from 158 · 39 (mean · SEM) off testosterone to 88 · 19 on testosterone therapy (P < 0.05). Hypercapnoeic ventilatory drive did not change significantly on testosterone. Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 · 3% to 22 · 2% when the men were receiving testosterone (P < 0.01), but the episodes of sleep apnoea tended to occur during non‐REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy. These results suggest that androgen levels present in normal man may play an important role in the pathogenesis of obstructive sleep apnoea.

Ventilatory Control in Myxedema and Hypothyroidism

Alveolar hypoventilation is known to occur in myxedema. To clarify the role of hypoxic ventilatory drive and hypercapnic ventilatory drive in thyroid hormone insufficiency states, 10 patients with myxedema and seven with hypothyroidism (thyroid ablation) were studied before and after thyroid replacement. An index developed for hypoxic ventilatory drive was markedly reduced in myxedema: 17 plus or minus 4.7 (S.E.M.) (normal, 126 plus or minus 8.7) (P smaller than 0.01) and increased to 78 plus or minus 12.6 (p = 0.02) with thyroid hormone replacement. In the hypothyroid group this index was also depressed as compared to normal at 67 plus or minus 20 (p smaller than 0.01) and increased to 114 plus or minus 19 (p smaller than 0.02) with replacement. An index for hypercapnic ventilatory drive was depressed in myxedema, 0.69 plus or minus 0.01), but was not significantly depressed in hypothyroidism. With thyroid hormone replacement this index did not significantly increase in either group. We conclude that both myxedema and hypothyroid states produce depression of hypoxic ventilatory drive that is responsive to replacement therapy. This alteration in ventilatory control may contribute to the hypoventilation seen in myxedema.

Obstructive sleep apnea syndrome induced by testosterone administration.

The obstructive sleep apnea syndrome is a recently described clinical disorder that results from repetitive episodes of upper-airway occlusion during sleep.1 Since the syndrome occurs much more fre...

Obesity and COPD: associated symptoms, health-related quality of life, and medication use.

Background: There is little data about the combined effects of COPD and obesity. We compared dyspnea, health-related quality of life (HRQoL), exacerbations, and inhaled medication use among patients who are overweight and obese to those of normal weight with COPD. Methods: We performed secondary data analysis on 364 Veterans with COPD. We categorized subjects by body mass index (BMI). We assessed dyspnea using the Medical Research Council (MRC) dyspnea scale and HRQoL using the St. Georges Respiratory Questionnaire. We identified treatment for an exacerbation and inhaled medication use in the past year. We used multiple logistic and linear regression models as appropriate, with adjustment for age, COPD severity, smoking status, and co-morbidities. Results: The majority of our population was male (n = 355, 98%) and either overweight (n = 115, 32%) or obese (n = 138, 38%). Obese and overweight subjects had better lung function (obese: mean FEV1 55.4% ±19.9% predicted, overweight: mean FEV1 50.0% ±20.4% predicted) than normal weight subjects (mean FEV1 44.2% ±19.4% predicted), yet obese subjects reported increased dyspnea [adjusted OR of MRC score ≥2 = 4.91 (95% CI 1.80, 13.39], poorer HRQoL, and were prescribed more inhaled medications than normal weight subjects. There was no difference in any outcome between overweight and normal weight patients. Conclusions: Despite having less severe lung disease, obese patients reported increased dyspnea and poorer HRQoL than normal weight patients. The greater number of inhaled medications prescribed for obese patients may represent overuse. Obese patients with COPD likely need alternative strategies for symptom control in addition to those currently recommended.

Comparison of high-frequency jet ventilation with conventional mechanical ventilation for bronchopleural fistula

In seven patients with acute respiratory failure and a bronchopleural fistula, the authors compared gas exchange and volume of gas lost via the chest tube during conventional mechanical ventilation (CV) and high-frequency jet ventilation (HFJV). After the initial comparison, patients were randomized to HFJV or CV, unless one mode of ventilation was clearly superior based on preestablished criteria. In six of the seven patients, oxygenation deteriorated after the switch from CV to HFJV. The ratio of PaCO2 to FIO2 declined from 227 ± 167 to 133 ± 100 (mean ± SD, P > 0.05), and the Paco2 increased from 47 ± 13 to 56 ± 18 mm Hg (P > 0.05). The mean chest tube leak did not change significantly. Randomization of the mode of ventilation was not performed in any patient because CV was superior by a priori criteria. We conclude that when acute respiratory failure is complicated by a bronchopleural fistula, HFJV with mean airway pressures comparable to those provided during conventional ventilation does not provide satisfactory gas exchange.

Patient-Ventilator Interaction

Patient-ventilator interaction has been the focus of increasing attention from both manufacturers and researchers during the last 25 years. There is now compelling evidence that passive (controlled) mechanical ventilation leads to respiratory muscle dysfunction and atrophy, prolonging the need for ventilatory support and predisposing to a number of adverse patient outcomes. Although there is consensus that the respiratory muscles should retain some activity during acute respiratory failure, patient-ventilator asynchrony is now recognized as a cause of ineffective ventilation, impaired gas exchange, lung overdistention, increased work of breathing, and patient discomfort. Far more common than previously recognized, it also predisposes to respiratory muscle dysfunction and other complications, leads to excessive use of sedation, increases the duration of ventilatory support, and interferes with weaning. Appropriate recognition and management of patient-ventilator asynchrony require bedside assessment of ventilator graphics as well as direct patient observation. Among currently available ventilation modes and approaches, none has been shown to be clearly superior to all the others with respect to patient-ventilator interaction, and strongly held preferences among investigators have led to controversy and difficulties in carrying out appropriate studies evaluating them. As a result, marked practice variation exists among different specialties as well as in different institutions and geographical areas. The respected authorities on mechanical ventilation who participated in this conference differed in the modes they preferred but agreed that proper understanding and use according to the individual patients needs are more important than which mode is chosen. Conference participants discussed the determinants, manifestations, and epidemiology of patient-ventilator asynchrony, and described and compared several ventilation modes aimed specifically at preventing and ameliorating it. The papers arising from these discussions represent the most thorough examination of this important aspect of respiratory care yet published.

Tuberculous Pleural Effusion

Tuberculous pleural effusion occurs in approximately 5% of patients with Mycobacterium tuberculosis (TB) infection[1][1] and accounts for 4% of all TB cases in the United States.[2][2] Diagnosis is challenging, with 48–96% of tuberculous pleural effusions negative by sputum acid-fast bacilli (AFB

Pulse Oximetry versus Arterial Blood Gas Specimens in Long-term Oxygen Therapy

Portable pulse oximeters are now widely available for the assessment of arterial oxygenation, and the U.S. Medicare program considers saturation readings to be acceptable substitutes for arterial PO2 in selecting patients for long-term oxygen therapy (LTOT). Current oximeters are reasonably accurate (plus or minus 4 or 5 percent of the co-oximetry value), but the clinician should be aware of several potential problems. Readings may be inaccurate in the presence of hemodynamic instability, carboxyhemoglobinemia, jaundice, or dark skin pigmentation, and also during exercise. Indicated saturation may substantially overestimate arterial PO2 if the patient is alkalemic. Pulse oximetry cannot detect hypercapnia or acidosis. For these and other reasons, pulse oximetry should not be used in initial selection of patients for LTOT, as a substitute for arterial blood gas analysis in the evaluation of patients with undiagnosed respiratory disease, during formal cardiopulmonary exercise testing, or in the presence of an acute exacerbation. Pulse oximetry is an important addition to the clinician’s armamentarium, however, for titrating the oxygen dose in stable patients, in assessing patients for desaturation during exercise, for sleep studies, and for in-home monitoring.

Translating Evidence Into Practice

Appropriately designed and conducted research is necessary for improving patient care and optimizing health outcomes, but access to best evidence is not enough to make these things happen. In respiratory care, as in other fields, patients do not benefit as much as they should from research findings and evidence-based practice guidelines. Current standards for the diagnosis, staging, and management of chronic obstructive pulmonary disease are based in large part on the results of spirometry, yet most patients carrying this diagnosis have not had this test performed. Despite compelling evidence that it saves lives, reduces complications, and decreases costs in acute respiratory failure complicating chronic obstructive pulmonary disease, noninvasive ventilation is not used in a large proportion of such cases. Lung-protective ventilation for acute lung injury and the acute respiratory distress syndrome also increases survival, decreases complications, and is cost-effective, yet many patients who stand to benefit do not receive it. Clinicians may not be aware of practice guidelines or be familiar with their recommendations; they may not agree with the recommendations, or have insufficient expectation that management according to the guideline will work; they may consider the guideline too complicated or difficult to use in their own practices; patient-related factors may interfere; and changing established practice is often difficult. Overcoming these and other barriers to best practice is the focus of knowledge translation, which recognizes the need for involvement of every aspect of health care and seeks to integrate them effectively. This paper discusses the challenges faced by knowledge translation, provides examples of its successful application in respiratory care, and summarizes what needs to be done if the potential benefits of available evidence are to be realized for both individual patients and the health care system as a whole.We are at a crucial stage in understanding the issues involved in translating public health evidence for urban planning and transport planning into practice. The city is now the preferred human habitat, yet we seem to be building into its very fabric complex challenges to health. The rise in non-communicable disease, increase in health inequity and the need to better support wellbeing are global concerns. Although we are generating public health evidence in an attempt to provide solutions, the gap between what we think we know, and what we do, never seems to get any narrower. This chapter explores the tensions and the arguments and proposes possible solutions for those involved in this struggle, be they researchers or practitioners. The city is the laboratory for change and the subject. But its complexity and its adaptability make it a laboratory like no other. And as a subject, it responds to our interventions with unpredictability. We need a new transdisiplinary science, not the business as usual of built environment and transport, and beyond the traditional evidence hierarchy of the public health world. New actors and new approaches are needed in the research arena. We need strong advocacy to support good evidence. We need to blend tactical urbanism with action research. And for that sake of future population health; city leadership, from many quarters, needs to learn how to collaborate for co-generation of new knowledge that will make a difference to people’s lives.