Use of Benzoctamine as Sedative in Patients with Respiratory Failure

Benzoctamine (Tacitin) was given by mouth as night sedation to patients admitted to hospital with respiratory failure. Fourteen patients had chronic obstructive bronchitis and six had acute severe asthma. One patient with asthma needed intravenous sedation with benzoctamine. No adverse effects were observed, and there was no significant change of forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), or Pco₂ in any patient after benzoctamine. Nevertheless, further clinical experience of the drug is required before its use can be safely recommended in respiratory failure.     

Long-term and Short-term Effects of Oral Prethcamide in Chronic Ventilatory Failure

The effect of oral prethcamide (Micoren) (a mixture of two related amides of crotonyl N′ butyric acid) was compared with a placebo preparation in 13 patients with established chronic ventilatory failure. Part I of the study comprised a double-blind single cross-over trial with an initial assessment and two further assessments at the end of each period of one month. Prethcamide was taken in 200-mg. doses four times daily. No subjective or objective changes were noted, and in particular the resting Pco₂ showed no change.Part II of the study comprised a double-blind single cross-over trial of the short-term effect of prethcamide compared with placebo in 12 patients in chronic ventilatory failure. Frequent estimations of mixed venous Pco₂ were made with a rebreathing technique for four and a half hours after ingestion of prethcamide or placebo preparation.Following prethcamide a fall in Pco₂ level to a minimum value at 30 minutes of 93% of control values and persisting for about three hours was noted for the group as a whole. The fall represents a lowering by about 4 mm. Hg of the mixed venous Pco₂.It is concluded that, though in patients with chronic ventilatory failure prethcamide may reduce the Pco₂ in the short term, there is no subjective benefit or observable objective change following repeated administrations over a period of one month.     

Mixed Venous and Arterial Pco2

The rebreathing method of measuring oxygenated mixed venous Pco₂ (P$\bar{v}$co₂) was originally introduced as a bloodless way to estimate arterial Pco₂ (Paco₂). It has become common practice to subtract 6 mm Hg from the P$\bar{v}$co₂ to obtain the Paco₂ but there are many circumstances in which this leads to an overestimate of the Paco₂. Measurements of P$\bar{v}$co₂ and Paco₂ in 19 patients have shown that a better approximation to Paco₂ under normal conditions of cardiac output and arterial O₂ saturation is Paco₂ = 0·8 P$\bar{v}$co₂. These studies also showed that the P$\bar{v}$co₂ — Paco₂ difference may be much wider, particularly in the presence of arterial unsaturation and a low cardiac output.The factors governing the venoarterial Pco₂ difference are reviewed and their magnitude is calculated to emphasize the complementary roles of measurements of P$\bar{v}$co₂ and Paco₂ in the assessment of patients with cardiorespiratory disease.     

Effect of Controlled Oxygen Therapy on Arterial Blood Gases in Acute Respiratory Failure

Seven patients in acute exacerbation of chronic respiratory failure were given 24·5% and later 28% oxygen through Ventimasks. The mean increases in arterial PO₂ were 11 and 21 mm. Hg while breathing 24·5% and 28% oxygen respectively compared with control values while breathing air. Associated increases in arterial PCO₂ were 4 and 8 mm. Hg, respectively. In five of the patients these increases in inspired oxygen concentration resulted in useful increases in tissue oxygen supply without significant deterioration in ventilation, but in two patients arterial PCO₂ rose excessively and artificial ventilation was required.     

Negative Pressure Artificial Respiration: Use in Treatment of Respiratory Distress Syndrome of the Newborn

Forty-five newborn infants in respiratory failure with respiratory distress syndrome were treated with intermittent negative pressure ventilation (INPV). There was a survival rate of 38% (17/45).All infants were initially treated without nasotracheal intubation. However, 24 of these developed a Paco₂ greater than 70 mm. Hg and were subsequently intubated. Intubation was followed by a decrease in the degree of hypercarbia in each instance and simultaneous increase in Pao₂.Complications encountered during ventilation were: emphysema (one patient), aspiration pneumonia (two patients), septicemia (two patients), misplaced nasotracheal tube (one patient).Follow-up of the 17 surviving patients for periods of four to 36 months disclosed two patients with post-intubation hoarseness. One infant initially had spastic quadriplegia with EEG abnormalities, both of which cleared by 5 months of age. In the remaining 14 infants, the results of physical, neurological and psychological examinations have remained within normal limits.     

慢性阻塞性肺疾病不同表型患者CAT评分与肺功能及预后的相关性分析

摘要 目的：探讨慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）不同表型评估测试问卷（COPD assessment test,CAT）评分与肺功能及预后的关系。方法：收集361例COPD患者临床资料、CAT评分、肺功能检查结果及肺外合并症、肺内并发症等情况,按临床表型分为肺气肿组（n=200）和支气管炎组（n=161）,分析肺气肿组200例和支气管炎组161例COPD患者CAT评分与肺功能及预后的关系。结果：肺气肿组CAT评分高于支气管炎组（P<0.05）,一秒用力呼气容积（FEV₁）占预计值百分比（FEV₁%）、FEV₁/用力肺活量（FVC）低于支气管炎组（P<0.05）,吸气分数（IC/TLC）低于支气管炎组,残总比（RV/TLC）高于支气管炎组（P<0.05）;肺气肿组肺间质性病变、肺动脉高压发生率均高于支气管炎组（P<0.05）;支气管炎、肺气肿组CAT评分均与FEV₁%、FEV₁/FVC、IC/TLC呈负相关（P<0.05）,与RV/TLC呈正相关（P<0.05）,肺气肿各参数相关度更高（P<0.05）;肺气肿组不同CAT评分患者肺间质性病变、肺动脉高压发生率比较差异有统计学意义（P<0.05）,支气管炎组不同CAT评分肺动脉高压发生率比较差异有统计学意义（P<0.05）,随CAT评分的升高,肺气肿组肺间质性病变、肺动脉高压发生率上升,支气管炎组肺动脉高压发生率上升。结论： COPD肺气肿表型CAT评分较支气管炎表型高,肺功能降低更明显,呈现肺过度通气,气流受限特点,更易并发肺间质纤维化、肺动脉高压,且与CAT评分变化密切相关。     

Regional Lung Function in Patients with Obstructive Lung Diseases

Regional lung function was measured, using radioactive xenon-133, in a group of normal subjects and in three carefully defined groups of patients with obstructive lung disease. When compared with the normal subjects, patients in the emphysematous group showed a relative reduction of ventilation and perfusion to the upper zones, while patients having chronic bronchitis without cardiac or respiratory failure showed a predominantly lower zone defect. In the group of patients with chronic bronchitis with cardiac and respiratory failure no consistent pattern was found.     

慢阻肺伴左心衰竭临床特征与影响因素分析

摘要 目的：探讨慢阻肺伴左心衰竭临床特征与影响因素。方法：回顾性选择2019年1月至2020年12月来我院诊治的慢性阻塞性肺疾病患者150例。根据是否合并心衰,将150例患者分为慢阻肺伴左心衰竭组（A组）与慢阻肺未伴左心衰竭组（B组）。分析150例患者中慢阻肺伴左心衰竭的占比,分析对比两组一般资料、习惯和疾病病史、肺功能、心脏彩超、心电图结果、血液指标水平与动脉血气指标,采用Logistic回归分析慢阻肺伴左心衰竭的影响因素。结果：（1）150例患者中,慢阻肺伴左心衰竭者占比为32.00 %,慢性阻塞性肺疾病未合并左心衰竭者占比为68.00 %。（2）两组性别、年龄、患病时间、糖尿病史、吸烟史、高血压史、冠心病史、FEV1/FVC、左房内径、左心室舒张末内径、左室重量分数、左室后壁厚度、肺动脉压、血小板计数、C反应蛋白、降钙素原、凝血酶原时间、D-二聚体、白蛋白、肌酸激酶同工酶、N末端脑钠肽前体、PaCO₂、PaO₂、SaO₂对比有差异（P<0.05）。（3）Logistic回归分析结果表明、性别、年龄、糖尿病史、吸烟史、高血压史、冠心病史、左心室舒张末内径、肺动脉压是影响慢阻肺合并左心衰竭患者的影响因素（P<0.05）。结论：慢阻肺伴左心衰竭的占比较高,其与性别为男性、年龄偏大、有糖尿病史、吸烟史、高血压史、冠心病史、左心室舒张末内径升高、肺动脉压升高相关,需对以上因素给予积极干预及治疗。     

Negative Pressure Artificial Respiration: Use in Treatment of Respiratory Failure of the Newborn

Ninety-one infants with respiratory failure secondary to primary pulmonary disease and with a birth weight of 1000 g. or over have been managed in a negative-pressure respirator (Air-Shields) over a three-year period. Of these the failure in 87 was due to respiratory distress syndrome (RDS) and in four it resulted from massive meconium aspiration. Respiratory failure was indicated initially by arterial blood gas tensions (while breathing 100% O₂) of Po₂ <40 mm. Hg, pH <7.10 and Pco₂ >75 mm. Hg in the initial 47 cases; these levels were subsequently raised to Po₂ < 50 mm. Hg, pH <7.20 and Pco₂ >70 mm. Hg for the remainder. Fifty-four (59.3%) of the infants survived the use of the respirator and 47 of these (51.6%) were subsequently discharged alive and well. Mean time in hours to normalization of blood gas values while on the respirator were as follows: for Po₂, 10.5; for pH, 11.6; and for Pco₂, 22.6. These values indicate that the respirator is more efficient in promoting oxygenation (raising Po₂) than ventilation (lowering Pco₂). They also suggest that the observed acidosis is in large part secondary to the hypoxia rather than the result of co₂ retention. For the survivors the average time of total respirator dependency before commencement of weaning was 53.7 hours. All the infants were managed without the use of endotracheal tubes although the use of the respirator and/or administration of 100% oxygen were either continuous or intermittent for periods of up to two weeks. There have been no instances of so-called respirator lung disease in the survivors or in those who died, which suggests that the use of high oxygen concentration by itself is not the major factor in the pathogenesis of this complication.     

Oxygen as a driving gas for nebulisers: safe or dangerous?

Changes in blood gas tensions occurring when 100% oxygen or air was used as the driving gas for nebulised salbutamol were studied in 23 patients with severe airways obstruction. The patients fell into three groups: nine had chronic bronchitis and emphysema with carbon dioxide retention, seven had emphysema and chronic bronchitis without carbon dioxide retention, and seven had severe asthma (no carbon dioxide retention). When oxygen was used as the driving gas patients who retained carbon dioxide showed a mean rise of 1.03 kPa (7.7 mm Hg) in their pressure of carbon dioxide (Pco2) after 15 minutes (p less than 0.001) but the Pco2 returned to baseline values within 20 minutes of stopping the nebuliser. The other two groups showed no rise in Pco2 with oxygen. When air was used as the driving gas none of the groups became significantly more hypoxic. Although it is safe to use oxygen as the driving gas for nebulisers in patients with obstructive airways disease with normal Pco2, caution should be exercised in those who already have carbon dioxide retention.     

Viral Antibody Levels and Clinical Status in Acute Exacerbations of Chronic Bronchitis: a Controlled Prospective Study

A controlled prospective study was made of a group of patients with chronic bronchitis, in which serum antibodies against a group of viruses and Mycoplasma pneumoniae were estimated at regular intervals. Sixteen significant rises in antibody titre were shown, of which eight were associated with clinical acute exacerbations of bronchitis. In individual patients no correlation was found between the number of acute exacerbations or the aetiological agent and persistent change in ventilatory function as expressed by the F.E.V._0.75.This study was compared with the results of a previous parallel investigation of the same patients done to study the significance of rhinovirus infections. In the present investigation 12% of the acute exacerbations were associated with the 11 agents tested compared with 14% associated with rhinoviruses in the earlier work.     

Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease – study protocol for a randomised controlled trial [ISRCTN11611768]

Background

We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children.

Methods

Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P_0.1) was measured in all conditions. The slope of the relation between P_0.1 and the partial pressure of end-tidal O₂ or CO₂ (P_ETO₂ and P_ETCO₂) served as the index of hypoxic or hypercapnic ventilatory drive.

Results

Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting P_ETCO₂ was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO₂ retention.

Conclusions

In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting P_ETCO₂. Whether or not diminished hypoxic drive or resting CO₂ retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO₂ retention are associated with sleep-disordered breathing in 6–12 year old children.     

Gill ventilation and O2 extraction during graded hypoxia in two ecologically distinct species of flatfish,the flounder (Platichthys flesus) and the plaice (Pleuronectes platessa)

Synopsis Gill ventilation, breathing frequency, breath volume, oxygen extraction from the ventilatory water current and oxygen uptake through the gills were measured in flounder, Platichthys flesus, and plaice, Pleuronectes platessa, at water O₂ tensions ranging from 35 to 155 mm Hg at 10° C. Ventilation volumes were similar in the two species at high water O₂ tension. Exposure to hypoxic water elicited a larger increase in ventilation in the flounder. The per cent extraction of O₂ from water decreased slightly in both species as water O₂ tension was lowered. At comparable levels of ventilation O₂ extraction was higher in flounder. At the higher levels of water O₂ tension, O₂ uptake across the gills of flounder was stable, the critical O₂ tension being between 60 and 100 mm Hg. The plaice behaved as an oxygen conformer over the entire range of O₂ tensions investigated. The superior ability of the flounder in maintaining OZ uptake across the gills during a reduction in water O₂ tension may in part explain why the species, unlike plaice, inhabits very shallow waters with large fluctuations in dissolved oxygen.     

The Prevalence of Chronic Respiratory Disease in the Male Physicians of London,Ontario

a survey of respiratory disease among male physicians of London, Ontario, resulted in a 96.3% response.The age-standardized rates of chronic bronchitis were not very different from others reported in the recent medical literature, taking into account smoking habits, but the overall prevalence of bronchial asthma was high (7.4%), with a low prevalence in the category “obstructive lung disease”. The possibility of overlap or interchange in these diagnoses is raised, although the diagnosis of bronchial asthma in this particular group is believed to be well established in every case.A history of seasonal hay fever was given by 19.4%.One of 88 (1%) non-smokers had bronchitis, whereas six of them (7%) had asthma.Rhonchi heard in the chest, on a single examination, appeared to be most closely related to current smoking habits, ventilatory function tests and also to a clinical diagnosis of chronic bronchitis or obstructive lung disease, but not to bronchial asthma.     

The influence of dissolved oxygen concentration on phosphofructokinase and the glucose metabolism ofEscherichia coli K-12

The glucose metabolism and the response of phosphofructokinase activity to oxygen were investigated using glucose-limited chemostat cultures ofE. coli K-12. With a dilution rate of 0.2 hr^–1 and a glucose input concentration of 0.83 g/litre, 10 steady states were obtained ranging from 320 to 0 mm HgO₂. Dissolved oxygen reached zero level at a pO₂ of 25.8 mm Hg. The specific phosphofructokinase activity was constant above 28 mm Hg O₂ and increased linearly at lower pO₂ levels until it reached highest activity at 0 mm Hg O₂. Cell dry weight also started to decrease linearly from 28 to 5.9 mm Hg O₂, and fell sharply thereafter. Acid production rate did not start before pO₂ reached 25.6 mm Hg, increased progressively with an additional sharp increase below 5.9 mm Hg O₂. The main endproducts formed were acetic acid and ethanol with lactic acid appearing below 5.9 mm Hg O₂. The results suggest an effect of oxygen on phosphofructokinase synthesis rather than an ATP inhibition of the enzyme.This work was supported by a grant from the Australian Research Grant Commission.     

Human Lung Homotransplantation

Left lung homotransplantation was performed in a 31-year-old man in terminal irreversible respiratory failure due to advanced silicosis. Within 10 minutes of completion of transplantation, arterial pO₂ rose from 52 to 211 mm. Hg, pCO₂ dropped from 90 to 43 mm. Hg, and pH rose from 7.15 to 7.42. On assisted ventilation, arterial O₂ tension was maintained within normal limits for the first four days. Thereafter, arterio-alveolar difference for O₂ increased to 300 mm. and that for CO₂ to 25 mm. Xenon-133 ventilation perfusion ratios confirmed differences between the two lungs. Terminally, bronchopneumonia and hypoxemia were present. Surfactant content of the lung was within normal limits. Postmortem examination revealed bronchopneumonia, bronchial infarction, lymphatic engorgement and mild rejection. Future efforts should emphasize selection of non-infected donors, minimal reliance on steroids for immunosuppression, cardiopulmonary bypass during transplantation, and more definite criteria for rejection.     

Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review

ObjectiveTo assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease.DesignSystematic review of randomised controlled trials that compared at least two months of regular oral mucolytic drugs with placebo.StudiesTwenty three randomised controlled trials in outpatients in Europe and United States.ResultsCompared with placebo, the number of exacerbations was significantly reduced in subjects taking oral mucolytics (weighted mean difference −0.07 per month, 95% confidence interval −0.08 to −0.05, P<0.0001). Based on the annualised rate of exacerbations in the control subjects of 2.7 a year, this is a 29% reduction. The number needed to treat for one subject to have no exacerbation in the study period would be 6. Days of illness also fell (weighted mean difference −0.56, −0.77 to −0.35, P<0.0001). The number of subjects who had no exacerbations in the study period was greater in the mucolytic group (odds ratio 2.22, 95% confidence interval 1.93 to 2.54, P<0.0001). There was no difference in lung function or in adverse events reported between treatments.ConclusionsIn chronic bronchitis and chronic obstructive pulmonary disease, treatment with mucolytics is associated with a reduction in acute exacerbations and days of illness. As these drugs have to be taken long term, they could be most useful in patients who have repeated, prolonged, or severe exacerbations of chronic obstructive pulmonary disease.

What is already know on this topic

Mucolytic drugs have properties that may be beneficial in chronic obstructive pulmonary diseaseThese drugs are not prescribed in the United Kingdom and Australasia, although they are widely used in many other countriesDrugs that reduce exacerbations may reduce the morbidity and healthcare costs associated with progressively severe disease

What this study adds

Regular use of mucolytic drugs for at least two months significantly reduces exacerbations and days of illness compared with placebo in patients with chronic bronchitis and chronic obstructive pulmonary diseaseExacerbations that do occur may not be as severe, and the benefit may be greater in those with more severe diseaseReductions are modest and treatment may not be cost effective     

Metabolic and ventilatory responses to hypoxia in two altitudinal populations of the toad, Bufo bankorensis

Effects of hypoxia on resting oxygen consumption ( ), lung ventilation, and heart rate at different ambient P_O2 were compared between lowland and high altitude populations of the toad, Bufo bankorensis. Resting decreased significantly in mild hypoxia (P_O2=120 mm Hg) at 10°C and in moderate hypoxia (P_O2=80 mm Hg) at 25°C in both altitudinal populations; however, resting did not differ significantly between the two populations. Numbers of lung ventilation periods (VP) and total inspired volume (V_L) did not change with P_O2 at 10°C, but did increase at moderate and severe hypoxia (40 mm Hg), respectively, at 25°C. Resting heart rates did not change during hypoxia and did not differ between altitude populations. The results suggest (1) the effect of P_O2 change on should be considered in future studies involving transfer of anurans to a different altitude; and (2) the metabolic and ventilatory physiology in B. bankorensis does not compensate for the low temperature and P_O2 at high altitude.     

Surfactant Therapy for Patients with ARDS After Cardiac Surgery

This multicenter study investigated the possibility of reducing mortality rate by administering natural lung surfactant additional to standard therapy to treat patients after cardiac surgery who developed an acute respiratory failure (ARDS/ALI).

A total of 78 patients (1998–2002) diagnosed with ALI or ARDS were enrolled in the study; patients were considered for study entry only if they developed ALI/ARDS within 72h after cardiac surgery. A total of 36 patients (2000–2002) received Surfactant-BL via bronchoscope at a dose of 3 mg/kg twice a day, and 42 patients (1998–2000) served as the historical control.

Within 24h after the first Surfactant-BL administration the PaO₂/FiO₂ ratio increased from (mean ± SEM) 129.7 ± 9.9 mm Hg to 187.6 ± 17.6 mm Hg (p < 0.01), FiO₂ decreased from (mean ± SEM) 0.71 ± 0.03 to 0.56 ± 0.03 (p < 0.01), and 69.4% of the patients treated with surfactant were weaned from the ventilator compared with 50% of the control group during a 28-day period. The mortality rate among patients treated with Surfactant-BL was 30.6% compared with 50% in the control group.

In conclusion, early administration of Surfactant-BL leads to the reduction of mortality in cardiac patients who develop postoperatively an ALI or ARDS.     

Cigarette Smoke-induced Ca2+ Release Leads to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Dysfunction

Chronic obstructive pulmonary disease affects 64 million people and is currently the fourth leading cause of death worldwide. Chronic obstructive pulmonary disease includes both emphysema and chronic bronchitis, and in the case of chronic bronchitis represents an inflammatory response of the airways that is associated with mucus hypersecretion and obstruction of small airways. Recently, it has emerged that exposure to cigarette smoke (CS) leads to an inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channel, causing airway surface liquid dehydration, which may play a role in the development of chronic bronchitis. CS rapidly clears CFTR from the plasma membrane and causes it to be deposited into aggresome-like compartments. However, little is known about the mechanism(s) responsible for the internalization of CFTR following CS exposure. Our studies revealed that CS triggered a rise in cytoplasmic Ca²⁺ that may have emanated from lysosomes. Furthermore, chelation of cytoplasmic Ca²⁺, but not inhibition of protein kinases/phosphatases, prevented CS-induced CFTR internalization. The macrolide antibiotic bafilomycin A1 inhibited CS-induced Ca²⁺ release and prevented CFTR clearance from the plasma membrane, further linking cytoplasmic Ca²⁺ and CFTR internalization. We hypothesize that CS-induced Ca²⁺ release prevents normal sorting/degradation of CFTR and causes internalized CFTR to reroute to aggresomes. Our data provide mechanistic insight into the potentially deleterious effects of CS on airway epithelia and outline a hitherto unrecognized signaling event triggered by CS that may affect the long term transition of the lung into a hyper-inflammatory/dehydrated environment.