Brydon J. B. Grant

Sleep-Disordered Breathing and Chronic Opioid Therapy

OBJECTIVE To assess the relation between medications prescribed for chronic pain and sleep apnea. DESIGN An observational study of chronic pain patients on opioid therapy who received overnight polysomnographies. Generalized linear models determined whether a dose relation exists between methadone, nonmethadone opioids, and benzodiazepines and the indices measuring sleep apnea. SETTING A private clinic specializing in the treatment of chronic pain. PATIENTS Polysomnography was sought for all consecutive (392) patients on around-the-clock opioid therapy for at least 6 months with a stable dose for at least 4 weeks. Of these, 147 polysomnographies were completed (189 patients declined, 56 were directed to other sleep laboratories by insurance companies, and data were incomplete for seven patients). Available data were analyzed on 140 patients. OUTCOME MEASURES The apnea-hypopnea index to assess overall severity of sleep apnea and the central apnea index to assess central sleep apnea. RESULTS The apnea-hypopnea index was abnormal (> or =5 per hour) in 75% of patients (39% had obstructive sleep apnea, 4% had sleep apnea of indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea); 25% had no sleep apnea. We found a direct relation between the apnea-hypopnea index and the daily dosage of methadone (P = 0.002) but not to other around-the-clock opioids. We found a direct relation between the central apnea index and the daily dosage of methadone (P = 0.008) and also with benzodiazepines (P = 0.004). CONCLUSIONS Sleep-disordered breathing was common in chronic pain patients on opioids. The dose-response relation of sleep apnea to methadone and benzodiazepines calls for increased vigilance.

Noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index ≥35 kg·m-2) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9–29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study.

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of <90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4±3.2 versus 7.4±2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5±0.3 versus 1.2±0.3 μmol·L−1), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.

Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD.

Objective:The objective of this study was to investigate the association between antioxidant nutrients and markers of oxidative stress with pulmonary function in persons with chronic airflow limitation.Design:Cross-sectional study exploring the association of antioxidant nutrients and markers of oxidative stress with forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%).Setting/Subjects:The study data included 218 persons with chronic airflow limitation recruited randomly from the general population of Erie and Niagara counties, New York State, USA.Results:After adjustment for covariates, multiple linear regression analysis showed that serum β-cryptoxanthin, lutein/zeaxanthin, and retinol, and dietary β-carotene, β-cryptoxanthin, lutein/zeaxanthin, vitamin C, and lycopene were positively associated with FEV1% (P<0.05, all associations). Serum vitamins β-cryptoxanthin, lutein/zeaxanthin, and lycopene, and dietary β-cryptoxanthin, β-carotene, vitamin C, and lutein/zeaxanthin were positively associated with FVC% (P<0.05, all associations). Erythrocytic glutathione was negatively associated with FEV1%, while plasma thiobarbituric acid-reactive substances (TBARS) were negatively associated with FVC% (P<0.05).Conclusion:These results support the hypothesis that an imbalance in antioxidant/oxidant status is associated with chronic airflow limitation, and that dietary habits and/or oxidative stress play contributing roles.

Central Sleep Apnea Induced by Acute Ingestion of Opioids

OBJECTIVES Three cases are presented in which patients were using opioids as required for nonmalignant pain management and significant central sleep apnea developed. Patients in the first two cases had no evidence of sleep-related breathing disorders on polysomnography until they ingested an opioid for treatment of chronic pain during the night and severe central sleep apnea developed. The patient in our third case had established obstructive sleep apnea but experienced a significant number of central events after the ingestion of an opioid analgesic, leading to worsening severity of his underlying sleep-related breathing disorder. CONCLUSION The short-term ingestion of opioid analgesics can precipitate central sleep apnea in patients with chronic pain receiving long-term opiate therapy who otherwise show no evidence of central sleep apnea and have no cardiac or neurologic disease that would predispose them to central sleep apnea.

Association between anemia and quality of life in a population sample of individuals with chronic obstructive pulmonary disease

BackgroundSeveral studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease. However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD).MethodsThis is a post-hoc analysis of a study which enrolled a population of adults aged 35–79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000. In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels. We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia. To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures.ResultsIn the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs. 49.2 (SD 9.1); p < 0.0001]. Among patients with COPD (n = 495) the PF scores (39.9 vs. 45.4) and the PCS (41.9 vs. 45.9) were significantly lower in individuals with anemia compared to those without. In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003). There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD.ConclusionIn patients with moderate to very severe COPD anemia may be associated with worse HRQL. However, co-morbidities may explain part or all of this association in these patients.

Accuracy of autotitrating CPAP to estimate the residual Apnea–Hypopnea Index in patients with obstructive sleep apnea on treatment with autotitrating CPAP

ObjectiveAutotitrating continuous positive airway pressure (auto-CPAP) devices now have a smart card (a pocket-sized card with embedded integrated circuits which records data from the CPAP machine such as CPAP usage, CPAP pressure, large leak, etc.) which can estimate the Apnea–Hypopnea Index (AHI) on therapy. The aim of this study was to determine the accuracy of auto-CPAP in estimating the residual AHI in patients with obstructive sleep apnea (OSA) who were treated with auto-CPAP without a CPAP titration study.Patients and MethodsWe studied 99 patients with OSA from April 2005 to May 2007 who underwent a repeat sleep study using auto-CPAP. The estimated AHI from auto-CPAP was compared with the AHI from an overnight polysomnogram (PSG) on auto-CPAP using Bland–Altman plot and likelihood ratio analyses. A PSG AHI cutoff of five events per hour was used to differentiate patients optimally treated with auto-CPAP from those with residual OSA on therapy.ResultsBland and Altman analysis showed good agreement between auto-CPAP AHI and PSG AHI. There was no significant bias when smart card estimates of AHI at home were compared to smart card estimates obtained in the sleep laboratory. An auto-CPAP cutoff for the AHI of six events per hour was shown to be optimal for differentiating patients with and without residual OSA with a sensitivity of 0.92 (95% confidence interval (CI) 0.76 to 0.98) and specificity of 0.90 (95% CI 0.82 to 0.95) with a positive likelihood ratio (LR) of 9.6 (95% CI 5.1 to 21.5) and a negative likelihood ratio of 0.085 (95% CI 0.02 to 0.25). Auto-CPAP AHI of eight events per hour yielded the optimal sensitivity (0.94, 95% CI 0.73 to 0.99) and specificity (0.90, 95% CI 0.82 to 0.95) with a positive LR of 9.6 (95% CI 5.23 to 20.31) and a negative LR of 0.065 (95% CI 0.004 to 0.279) to identify patients with a PSG AHI of  ≥ 10 events per hour.ConclusionAuto-CPAP estimate of AHI may be used to estimate residual AHI in patients with OSA of varying severity treated with auto-CPAP.

High-resolution CT findings in patients with pulmonary tuberculosis: correlation with the degree of smear positivity.

Background There are data about the relationship between morphologic findings on high-resolution computed tomography (HRCT) and the number of acid-fast bacilli (AFB) on sputum smears in patients with pulmonary tuberculosis (PTB). It was also shown that existence of cavities and airspace consolidation might be related to smear positivity in PTB patients. However, there is no study suggesting a relationship between AFB on sputum smears and radiologic extent of disease based on HRCT findings. Aim In this study, we investigated a relationship between the degree of smear positivity and radiologic extent of disease based on HRCT findings and, the degree of smear positivity and different pulmonary parenchymal changes on HRCTs of the PTB patients. Methods Sixty-one male patients with PTB (mean age: 22±3.2) were included into the study. HRCT images were assessed for patterns, distribution, and profusion of pulmonary abnormalities. Dividing the lungs into 3 zones, profusion of abnormalities was assessed. A profusion score was given. Patients were divided as smear positive and smear negative and compared for the scores of HRCT findings. Smear-positive patients were divided into 4 groups as per grading of the sputum AFB smear: group I (sputum 1+), group II (sputum 2+), group III (sputum 3+), and group IV (sputum 4+). Correlations were investigated between the degree of smear positivity and the scores of HRCT findings. Results A significant correlation between radiologic extent of the disease based on HRCT and the degree of smear positivity was found (r=0.63, P=0.0001). There were also significant correlations between the degree of smear positivity and the scores of different HRCT findings. Nodule, cavity, and bronchial lesions are the most important contributors of the predictive properties of the total score. There was significant differences for the scores of HRCT findings between smear-positive and smear-negative patients. Conclusions Our study suggests that radiologic extent of disease based on HRCT findings in patients with PTB correlated with the degree of smear positivity. Different HRCT findings such as nodule, cavitation, ground-glass opacity, consolidation, and bronchial lesion are significantly associated with smear-positive PTB. Particularly, nodules, cavities, and bronchial lesions might be predictors of smear positivity in patients with PTB. This study also suggests that the thickness of cavity wall and the distance of cavity from central airways might be related to the degree of smear positivity.

Post-graduation migration intentions of students of Lebanese medical schools: a survey study

BackgroundThe international migration of physicians is a global public health problem. Lebanon is a source country with the highest emigration factor in the Middle East and North Africa and the 7th highest in the World. Given that residency training abroad is a critical step in the migration of physicians, the objective of this study was to survey students of Lebanese medical schools about their intentions to train abroad and their post training plans.MethodsOur target population consisted of all students of Lebanese medical schools in the pre-final and final years of medical school. We developed the survey questionnaire based on the results of a qualitative study assessing the intentions and motives for students of Lebanese medical schools to train abroad. The questionnaire inquired about students demographic and educational characteristics, intention to train abroad, the chosen country of abroad training, and post-training intention of returning to Lebanon.ResultsOf 576 eligible students, 425 participated (73.8% response rate). 406 (95.5%) respondents intended to travel abroad either for specialty training (330 (77.6%)) or subspecialty training (76 (17.9%)). Intention to train abroad was associated with being single compared with being married. The top 4 destination countries were the US (301(74.1%)), France (49 (12.1%)), the United Kingdom (31 (7.6%)) and Canada (17 (4.2%)). One hundred and two (25.1%) respondents intended to return to Lebanon directly after finishing training abroad; 259 (63.8%) intended to return to Lebanon after working abroad temporarily for a varying number or years; 43 (10.6%) intended to never return to Lebanon. The intention to stay indefinitely abroad was associated male sex and having a 2nd citizenship. It was inversely associated with being a student of one of the French affiliated medical schools and a plan to train in a surgical specialty.ConclusionAn alarming percentage of students of Lebanese medical schools intend to migrate for post graduate training, mainly to the US. A minority intends to return directly to Lebanon after finishing training abroad.

CLINICAL SIGNIFICANCE OF PULMONARY ARTERIAL INPUT IMPEDANCE

Pulmonary arterial input impedance excites the attention of few clinicians, but there are compelling reasons why they should be more interested in this subject. Physicians are well-versed in the intricacies of pulmonary vascular resistance, which is a measure of the opposition to the mean components of flow. Impedance is a measure of the opposition to the pulsatile components of flow. Right ventricular afterload is usually considered in terms of pulmonary vascular resistance. Yet, between one third and one half of the hydraulic power in the main pulmonary artery is contained in the pulsatile components of flow [1]. Therefore, measurement of arterial input impedance is needed to obtain a complete description of ventricular afterload [2]. The primary cause of cor pulmonale is an increase in the right ventricular afterload [3]. Therefore, impedance is likely to make a substantial contribution to this perennial problem. Most pulmonary vascular research has focused on the small pulmonary arteries, which appear to be the main site of resistance. Impedance is dependent on the mechanical properties and the geometry of the proximal pulmonary arteries. The pulmonary arterial input impedance spectrum is dependent primarily on the first five orders from the main pulmonary artery in decreasing levels of importance [4]. The proximal pulmonary arteries are the first line of opposition to right ventricular output and have a dominant effect on the input impedance. The fact that the mean and the pulsatile components of flow are dependent on different portions of the pulmonary circulation suggests that they could be controlled separately, without much overlap. It seems likely that this may be an unexplored avenue that may open the possibility of developing new therapeutic interventions. Although the factors that affect pulmonary vascular resistance are many, resistance, unlike impedance, can be expressed as a single number. Impedance is a function of frequency and requires a graphical display of the spectrum to show its magnitude and the phase relation between pressure and flow over a range of frequencies that are contained in the measured pressure and flow waveforms. The magnitude of impedance varies with frequency because of wave reflection [5]. The pulmonary circulation is pulsatile with multiple bifurcations; wave reflection is an inevitable consequence. When the forward pressure wave from the heart collides with the backward pressure wave that was reflected from the bifurcations, pressure increases. In contrast, when the forward flow wave from the heart meets the backward flow wave that was reflected from the bifurcations, flow decreases. As a result of wave reflections, the pressure and flow waves are not in phase with each other. Although not easily appreciated clinically, except perhaps in severe pulmonary hypertension, wave reflection occurs even under physiological conditions. Pressure lags flow at normal cardiac frequency in normal subjects. Because resistance is the opposition to mean flow, it is represented by only one frequency, zero, and there is no phase relation to consider because it is zero, the mean pressure and mean flow change simultaneously under steady-state conditions. To circumvent the need for a display of the entire impedance spectrum and the associated complexity that occurs with a statistical evaluation, there have been several approaches to representing the essential features of the spectrum as one or two numbers. Some investigators have used lumped parameter models to represent impedance [6]. These models are simple electrical circuits of resistors, capacitors and inductors. The values of these elements are altered to produce an input impedance that is similar to the input impedance of the pulmonary circulation. The value of these elements has been shown to reflect certain aspects of the haemodynamic properties of the pulmonary vasculature. Nevertheless, the lumped parameter model has several drawbacks. For example, lumped parameter models do not have any explicit representation of wave reflection, although the elements responsible for its occurrence are represented. Wave reflection does not occur in the electrical circuit because current is transmitted instantaneously. To circumvent this limitation, others have used transmission line theory of fluid dynamics. Transmission line theory emphasizes the importance of characteristic impedance [7]. Characteristic impedance is the input impedance in the absence of wave reflection. Although wave reflection cannot be eliminated from the pulmonary circulation under normal circumstances, wave reflection is minimal at high frequencies. The viscoelastic properties of the vessel wall dampen wave propagation at these frequencies. As a result, the pressure and flow are in phase, so that the phase shift is close to zero and characteristic impedance can be represented by a single number. Theory indicates that it is dependent on the calibre and compliant properties of the main pulmonary artery. EDITORIAL