Continuous monitoring of pO2 by means of intravascular indwelling oxygen electrodes (author's transl)

Two intravascular oxygen electrodes (of the International Biophysics Corporation and Roche) were tested in vitro and in long-term monitoring of arterial oxygen partial pressure in 19 patients. There were no complications. Both electrodes proved suitable for use for monitoring in an intensive-care situation. But both could still be improved by having greater stability and a shorter response time. Some of the indications for continuous monitoring of pO2 are mentioned: incipient respiratory failure, shock-lung, pulmonary oedema, and artificial ventilation. Haemorrhagic diatheses and arterial occlusive disease are contra-indications to its use.     

Respiratory failure based on pulmonary tuberculosis sequelae and its management

According to the complexity of pathological change of pulmonary tuberculosis sequelae (TB seq), on which respiratory failure based shows the higher incidence of marked degree of hypoxemia and hypercapnia than that based on chronic pulmonary emphysema (CPE). In TB seq, pulmonary artery mean pressure is higher, nocturnal oxyhemoglobin desaturation is much lower than in CPE. Also hypoxemia on exercise is lower, and oxygen inhalation for this hypoxemia is more effective than in CPE. The most effective therapy is continuous oxygen therapy. Home oxygen therapy has improved the prognosis and quality of life (QOL) of patients with respiratory failure based on TB seq. Artificial positive pressure ventilation (TIPPV) with intubation or tracheotomy is carried out for patients with severe hypercapnia and respiratory acidosis. Recently, early application of nasal mask ventilation (NPPV) on patients with TB seq has prohibited acute exacerbation of chronic respiratory failure. And also for patients with severe hypercapnia, NPPV with BIPAP method is effective for their QOL. Comprehensive respiratory rehabilitation is also successfully applied for their management.     

Intravenous nitroglycerin in acute respiratory failure of patients with chronic obstructive lung disease, secondary pulmonary hypertension and cor pulmonale

We have studied the hemodynamic effects of an intravenous single dose of nitroglycerin in 13 patients with secondary pulmonary hypertension and Cor Pulmonale, during the acute course of respiratory failure and under assisted ventilation. We observed a significant decrease in systolic, diastolic and mean pulmonary arterial pressures, and in pulmonary resistance and systolic right ventricular work index, without any change in right or left pre-loads. The systolic arterial pressure decreased slightly, without any change in cardiac index or diastolic pressure. The arterial and mixed venous oxygen contents, and the pulmonary shunting ( Qs/Qt) were unchanged. These results suggest that nitroglycerin may be a useful therapy in patients in the acute stages of pulmonary hypertension resulting from chronic lung disease and under assisted ventilation. In addition, the lack of change in cardiac index, intrapulmonary shunting and oxygen content suggests that this decrease in pulmonary resistance is not linked with any deleterious effect in oxygen transfer.     

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.     

Venous leg ulcers. Part 1: Aetiology

Cardiogenic pulmonary edema is a frequent cause of reparatory failure. We investigated the effects of nasal continuous positive airway pressure (CPAP) in patients with severe pulmonary edema associated with acute myocardial infarction. Twenty-nine consecutive patients were divided into 3 groups: firstly, 7 intubated patients who received mechanical ventilation at study entry comprised the intubation group. The rest of the patients were randomly assigned to either of the following 2 groups: 11 patients who received oxygen plus CPAP delivered by a nasal mask (CPAP group), and 11 patients who received oxygen only via face mask (oxygen group). All patients in the intubation group had cardiogenic shock. Two patients (18%) in the CPAP group and 8 patients (73%) in the oxygen group required mechanical ventilation with endotracheal intubation (p=0.03). The hospital mortality rate in the CPAP group (9%) was significantly lower than the oxygen group (64%, p=0.02). The pulmonary artery wedge pressure and heart rate were significantly lower in the CPAP group than in the oxygen group 24 h after study entry (p<0.05 and p<0.01). The mean pulmonary artery pressure 48 h after study entry was 18+/-5 mmHg in the CPAP group and 25+/-8 mmHg in the oxygen group (p<0.05). The PaO2/FiO2 ratio increased in the intubation group (168+/-69 to 240+/-57, p<0.05) and the CPAP group (137+/-17 to 253+/-67, p<0.01) 24 h after study entry. Arterial plasma endothelin-1 concentrations decreased significantly earlier in the CPAP group than in the oxygen group (p<0.05). In patients without cardiogenic shock, nasal CPAP lead to an early improvement in oxygenation and hemodynamics, and decreased the mortality rate. Early and active respiratory management is recommended in patients with pulmonary edema associated with acute myocardial infarction.     

Effects of phospholipid base analogues on the subcellular membrane ether composition of suspension cultured LM cells

Morbidity and mortality from pulmonary complications following urinary tract operations can be reduced by preoperative identification of the high risk patient. Pulmonary function tests and arterial blood gases are necessary to identify these patients and to delineate the severity of their pulmonary disease. Respiratory complications can be prevented in many patients with the proper use of pre- and postoperative chest physical therapy and oxygen therapy. Despite the most careful pulmonary management, some patients develop acute respiratory failure following urologic operations. Respiratory failure results from a combination of physiologic abnormalities which impair alveolar ventilation and oxygenation. Utilizing controlled ventilation, supplemental oxygen, and a physiologic approach to treating the underlying cause of respiratory failure, three fourths of urologic patients in respiratory failure may be expected to survive.     

Use of non-invasive positive pressure ventilation for cardiogenic pulmonary edema in emergency care units

The work reported by L'Her et al. in this issue of La Presse Médicale demonstrates the feasibility of applying simple intensive care techniques in situations frequently encountered in emergency care units. These authors used a face mask for continuous positive pressure ventilation in patients over 70 years of age admitted for respiratory distress related to cardiogenic pulmonary edema. In these elderly patients, the authors noted an improvement in blood gases, respiratory rate and heart rate and did not observe any secondary effect. Acute respiratory failure was cured in 90% of the cases without referral to the intensive care unit. The mechanism of action of continuous positive airway pressure, or spontaneous ventilation with positive expiratory pressure, is different from simple oxygen therapy. Two mechanisms are intimately related. The main effect is ventilatory assistance resulting from a "re-aeration" of the pulmonary parenchyma which increases compliance and reduces work required to overcome elastic retraction forces. Likewise the increased pulmonary volume reduces pulmonary resistance. Positive airway pressure also has an effect on left ventricular function. Indeed, after-load is reduced by the reduction in the large negative intrathoracic pressure swing. Lower energy expenditure required for respiration also greatly reduces total oxygen consumption and improved blood gases favor oxygen supply to the myocardium. The contraindications of continuous positive airway pressure are related to abnormal control of the upper airways and major hemodynamic disorders. Prudence is also required in case of shock due to the risk of major respiratory muscle fatigue. The question could also be raised as to the risk in elderly patients where cardiogenic pulmonary edema is often associated with a certain degree of chronic bronchitis. It is now known that these patients have an intrinsic positive expiratory pressure which considerably increases respiratory work. Symptomatic treatment in this type of disorder is mechanical and continuous positive airway pressure diminishes this work. Cardiogenic pulmonary edema in the elderly is thus an excellent indication for spontaneous ventilation with positive expiratory pressure. Improvement in these simple techniques, their widespread use and a better understanding of their limitations remain important challenges for the future.     

Physiological changes occurring with positive pressure ventilation: Part Two

Although the physiological effects of positive pressure ventilation are numerous, sometimes undesirable and have varying degrees of significance, positive pressure ventilation still plays a major role in the resuscitation and treatment of critically ill patients. Advances in the various methods of delivering positive pressure, especially when incorporating spontaneous breathing, have reduced the severity of complications. Despite serious complications, mechanical ventilation has advantages. When it is instituted for ventilatory and hypoxaemic respiratory failure, the benefits can be viewed in the context of the work of breathing. Spontaneous breathing normally requires 5% of total oxygen delivery to meet its demands. In lung disease, the ratio of oxygen consumption by the respiratory muscles to whole body oxygen consumption can increase to 25-30% (Henning 1986, Pinksy 1990). Mechanical ventilation reduces the energy demand of respiratory muscles and increases the oxygen delivery to other vital organs. When mechanical ventilation improves hypoxaemia and/or hypercarbia, or significantly decreases the work of breathing, it may also normalize associated changes in heart rate (Perel & Pizov 1991 p53). When cardiac output is increased in response to the increased work of breathing and associated stress, the institution of mechanical ventilation may beneficially lower the cardiac output simply due to the decrease in oxygen demand; thus the physiological reduction in cardiac output may not necessarily be regarded as a complication. The effects of raised intrathoracic pressure during mechanical ventilation may be beneficial when used to prevent or reduce pulmonary oedema, though problematic in some other situations. Mechanical ventilation is a life-saving treatment which has many associated complications; nurses have to accept the unavoidable hazards and adapt their nursing care to minimize their effects.     

Traumatic uveitis: the problem of pathogenetic therapy

Inhalative nitric oxide (NO) has recently been included in the therapeutic armament for the treatment of ARDS. We evaluated the effect of inhalative NO on hemodynamic and oxygen transport parameters in 30 internal intensive care patients suffering from ARDS. All patients received a pulmonary artery catheter. Hemodynamics were assessed prior to NO therapy and after 1, 6, 12, and 24 h. 80% (n = 24) of the patients were classified as therapy responders. The median NO dose was 15 ppm (range 5 to 40 ppm). The PaO2/FiO2--ratio increased significantly after initiation of NO (p = 0.0002) while the pulmonary shunt fraction (Qs/Qt) decreased significantly (p = 0.0019). All other measured or calculated parameters including arterial and pulmonary arterial blood pressure remained unchanged. No negative effects of the therapy could be observed. Inhalative NO improves oxygenation in most intensive care patients with ARDS and thus offers the possibility to reduce invasiveness of mechanical ventilation.     

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.     

Metabolic support of collecting duct transport

This study investigated the impact of deep diaphragmatic breathing (DB) on blood gases, breathing pattern, pulmonary mechanics and dyspnoea in severe hypercapnic chronic obstructive pulmonary disease (COPD) patients recovering from an acute exacerbation. Transcutaneous partial pressure of carbon dioxide (Ptc,CO2) and oxygen (Ptc,O2) and arterial oxygen saturation (Sa,O2), were continuously monitored in 25 COPD patients with chronic hypercapnia, during natural breathing and DB. In eight of these patients, breathing pattern and minute ventilation (V'E) were also assessed by means of a respiratory inductance plethysmography. In five tracheostomized patients, breathing pattern and mechanics were assessed by means of a pneumotachograph/pressure transducer connected to an oesophageal balloon. Subjective rating of dyspnoea was performed by means of a visual analogue scale. In comparison to natural breathing deep DB was associated with a significant increase in Ptc,O2 and a significant decrease in Ptc,CO2, with a significant increase in tidal volume and a significant reduction in respiratory rate resulting in increased V'E. During DB, dyspnoea worsened significantly and inspiratory muscle effort increased, as demonstrated by an increase in oesophageal pressure swings, pressure-time product and work of breathing. We conclude that in severe chronic obstructive pulmonary disease patients with chronic hypercapnia, deep diaphragmatic breathing is associated with improvement of blood gases at the expense of a greater inspiratory muscle loading.     

Selective intrabronchial instillation of surfactant in a patient with pneumonia: a preliminary report

The efficacy of treatment with exogenous surfactant has been reported in children with respiratory failure due to severe pneumonia. Its effect in adults with similar features has not been established. We therefore administered 240 mg of surfactant to a 71 year old man, who had developed right lower lobe pneumonia and hypoxaemia following abdominal aortic surgery. After this treatment, the patient's oxygenation, evaluated by arterial oxygen tension/fraction of inspired oxygen (PaO2/FIO2) ratio during artificial ventilation, gradually improved, and ventilator settings could be reduced whilst maintaining PaO2 at the appropriate level. Although the precise mechanism by which surfactant improves respiratory failure due to pneumonia is unclear, administration of the drug may have overcome a quantitative deficiency of endogenous surfactant attributable to the antagonistic effect of pulmonary exudates and reduced production following damage to type II pneumocytes. The present case provides an indirect suggestion of a possible causal relationship between the improvement of oxygenation and administration of surfactant in adult respiratory failure caused by pneumonia.     

Nocturnal pulmonary hypertension in an elderly patient with sleep apnea syndrome

We report a case of sleep apnea syndrome (SAS) with nocturnal pulmonary hypertension (NPH) in a 71-year-old man suffering from dyspnea during sleep. Severe snoring at night and daytime sleepiness were noticed before admission by his wife. Nocturnal oxygen desaturation (NOD) was documented with a pulse oximeter and severe sleep apnea syndrome was diagnosed on the basis of results of respiratory inductive plethysmography, an apnea index (AI) > 20, minimum SpO2 56%. NPH was diagnosed by Swan-Ganz catheter. The levels of NPH were severe. Elevation of systolic pulmonary arterial pressure (PAP) above 40 mmHg was observed 137 episodes at night. Both NPH and NOD were improved by 1 L/min of nasal oxygen therapy. A number of episodes of systolic PAP above 40 mmHg with oxygen therapy was 55 episodes. Peak mean PAP was 36 mmHg in room air vs 33 mmHg in oxygen therapy. Minimum SpO2 with oxygen therapy was improved to 69%. Total time of SpO2 < 90% at night was 153 minutes in room air vs 37 minutes in oxygen therapy. In this case, NPH and NOD due to severe SAS were remarkably improved by oxygen therapy.     

Effects of inspiratory flow waveforms on arterial blood gases and respiratory mechanics after open heart surgery

The clinical usefulness of inspiratory flow pattern manipulation during mechanical ventilation remains unclear. The aim of this study was to investigate the effects of different inspiratory flow waveforms, i.e. constant, sinusoidal and decelerating, on arterial blood gases and respiratory mechanics, in mechanically ventilated patients. Eight patients recovering after open heart surgery for valvular replacement and/or coronary bypass were studied. The ventilator inspiratory flow waveform was changed according to a randomized sequence, keeping constant the other variables of the ventilator settings. We measured arterial blood gases, flow, volume and pressure at the proximal (airway opening pressure (Pao)) and distal (Ptr) ends of the endotracheal tubes before and after 30 min of mechanical ventilation with each inspiratory flow waveform. We computed breathing pattern, respiratory mechanics (pressures and dynamic elastance) and inspiratory work, which was then partitioned into its elastic and resistive components. We found that: 1) arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) were not affected by changes in the inspiratory flow waveform; and 2) peak Pao and Ptr were highest with sinusoidal inspiratory flow, whilst mean Pao and Ptr and total work of breathing were least with constant inspiratory flow, mainly because of a concomitant decrease in resistive work during constant flow inflation. The effects of the inspiratory flow profile on Pao, Ptr and total inspiratory work performed by the ventilator were mainly due to the resistive properties of the endotracheal tubes. We conclude that the ventilator inspiratory flow waveform can influence patients' respiratory mechanics, but has no impact on arterial oxygen and arterial carbon dioxide tension.     

Aerosolized prostacyclin and iloprost in severe pulmonary hypertension

OBJECTIVE: To compare the effects of aerosolization of prostacyclin and its stable analog iloprost with those of nasal oxygen, inhaled nitric oxide, and intravenous prostacyclin on hemodynamics and gas exchange in patients with severe pulmonary hypertension. DESIGN: Open uncontrolled trial. SETTING: Justus-Liebig-University, Giessen Germany. PATIENTS: 4 patients with primary pulmonary hypertension and 2 patients with severe pulmonary hypertension associated with calcinosis, the Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (the CREST syndrome). All were classified as New York Heart Association class III or class IV. INTERVENTION: Short-term applications of O2, inhaled nitric oxide, intravenous prostacyclin, aerosolized prostacyclin, and aerosolized iloprost during repeated catheter investigation of the right side of the heart within a 1-month period. One patient had long-term therapy with inhaled iloprost. RESULTS: Aerosolized prostacyclin decreased pulmonary artery pressure in 6 patients from (mean +/- SE) 62.3 +/- 4.1 mm Hg to 50.8 +/- 5.5 mm Hg and reduced pulmonary vascular resistance from 1721 +/- 253 dyne/s cm-5 to 1019 +/- 203 dyne/s cm-5, and it increased cardiac output from 2.75 +/- 0.21 L/min to 4.11 +/- 0.54 L/min, mixed venous oxygen saturation from 51.1% +/- 3/4% to 66.3% +/- 4.1% and arterial oxygen saturation from 90.6% +/- 2.7% to 93.8% +/- 23% (P<0.05 for all changes). Mean systemic arterial pressure was only slightly affected. The responses lasted for 10 to 30 minutes after inhalation was terminated. Aerosolized iloprost had an identical efficacy profile but was associated with a longer duration of the pulmonary vasodilatory effect (60 min to 120 min). In comparison, intravenous prostacyclin reduced pulmonary vascular resistance with corresponding efficacy but produced a more pronounced decline in systemic artery pressure and no clinically significant decrease in pulmonary artery pressure. Nitric oxide and O2 were less potent pulmonary vasodilators in these patients. In one patient, 1 year of therapy with aerosolized iloprost (100 microgram/d in six aerosol doses) resulted in sustained efficacy of the inhaled vasodilator regimen and clinical improvement. CONCLUSION: Aerosolization of prostacyclin or its stable analog iloprost causes selective pulmonary vasodilatation, increases cardiac output, and improves venous and arterial oxygenation in patients with severe pulmonary hypertension. Thus, it may offer a new strategy for treatment of this disease.     

Possible association of a silent polymorphism in the neuronal nicotinic acetylcholine receptor subunit alpha4 with common idiopathic generalized epilepsies

OBJECTIVE: In patients with chronic obstructive pulmonary disease (COPD), intratracheal oxygen insufflation (ITO) is an established therapeutic approach. We developed a new endoscopic technique of intratracheal catheter placement. The aim of this pilot study was to demonstrate its short-term feasibility in acutely extubated patients with moderate to severe COPD who require oxygen therapy. DESIGN: A guide wire was inserted through a nasally passed bronchoscope and was positioned such that its tip was placed intratracheally. Using a "Seldinger technique", the tracheal catheter was then inserted over the wire to a point 2-3 cm proximal to the carina and positioned under direct vision from the bronchoscope inserted through the contralateral nose. After catheter insertion, the guide wire was removed. The patients scored catheter-associated local discomfort using a visual analogue scale. In a randomly assigned, crossover design, the effectiveness of the endoscopically (e) inserted ITO catheter was assessed by measuring the capillary blood gases, respiratory rate (RR), tidal volume (Vt) and minute ventilation (MV) after 1 h breathing room air without eITO and 1 h after eITO (flow: 3 l/min). MEASUREMENTS AND RESULTS: The eITO catheter was placed in all patients without complications and with only minimal discomfort in two patients (spontaneously reversible cough). Compared to breathing room air, capillary O2 pressure increased (from 54.7 +/- 9.4 to 82.8 +/- 21.8 mmHg) whereas Vt (from 458.7 +/- 86.8 to 358.3 +/- 75.1 ml) and MV (from 7.7 +/- 1.5 to 5.5 +/- 1.1 l/ min) decreased significantly (each p < 0.0001) with eITO in all patients. The capillary CO2 pressure and RR did not change. CONCLUSIONS: Acutely extubated patients in whom oxygen therapy is indicated may profit from eITO. This new technique works immediately and is thus an effective short-term intervention of potential value in the intensive care unit.     

Evaluation of the respiratory function by lung scintigraphy in patients candidates for pulmonary resection

Sixty-one patients undergoing pulmonary resection were studied pre- and post-operatively by spirometry, arterial gas determination, and quantitative ventilation/perfusion lung scanning. Our results showed that ventilation and/or perfusional scintigraphic scanning is currently the most reliable method in identifying patients at risk for postoperative respiratory insufficiency. Specifically, this technique was successful in detecting pulmonary areas other than those to be resected presenting ventilation or perfusional abnormalities. Therefore, the technique is particularly useful in predicting residual pulmonary function.     

Factors influencing successful discontinuance of mechanical ventilation after open heart surgery: a clinical study of 41 patients

Circulatory, respiratory, and metabolic variables were measured with a mobile clinical bedside unit in 41 patients during the first 48 hours after open heart surgery. Calculations were carried out off-line by a computer program. The variables were measured during controlled mechanical ventilation and compared with those obtained during spontaneous breathing and after resumption of mechanical ventilation; attempts at spontaneous breathing were categorized as successful or unsuccessful. The variables were compared before, during, and after the successful and the unsuccessful attempts at spontaneous breathing. In the series as a whole, the onset of spontaneous breathing was characterized by increases in cardiac output, radial arterial and pulmonary arterial pressures, and mixed venous oxygen tension (PVO2) and content (CVO2), as well as diminished arterial and mixed venous oxygen content differences (avDO2); no significant changes in oxygen consumption (VO2) were seen. Unsuccessful attempts disturbed the patient's physiological equilibrium by reducing oxygen delivery and not increasing VO2, while increasing ventilatory work. In general, resumption of controlled ventilation restored the physiological variables to their control conditions. Successful attempts at spontaneous breathing did not greatly affect the physiological variables. The indication for resumption of controlled ventilation after periods of spontaneous breathing is the combination of increased ventilatory work with diminished circulatory and respiratory functions.     

Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat

Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p<0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p<0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p<0.01). The net result was a stimulation of ventilation at PET,CO2 <5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.     

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.