Ventilation-perfusion inequality in nocturnal hypoxaemia due to chronic obstructive lung disease (COLD)

Summary. Nocturnal hypoxaemia is often noted in COLD patients with a daytime PaO₂ above 8.0 kPa. It has been assumed that ventilation-perfusion inequality contributes to nocturnal hypoxaemia. 10 patients with advanced COLD [median FEV₁ 0.73 (range 0.50-1.32)1], but without daytime hypoxaemia [median PaO₂ 8.35 (range 8.0–12.2) kPa] were investigated with regard to possible nocturnal hypoxaemia using polysomnography. Daytime lung function was assessed by spirometry and carbon monoxide diffusion capacity (DL_CO). Daytime ventilation-perfusion (V_A/Q) relationships were measured by the multiple inert gas elimination technique. Dispersion of perfusion and ventilation distributions was increased [log SDQ 1.01 (range 0.80-1.35) and log SDV 0.91 (range 0.69-1.86) resp.]. Around 8% of the ventilation was directed towards high V_A/Q areas (10< V_A/Q<100). All subjects reached all sleep stages, and all but one had a nadir nocturnal oxygen saturation (SaO2) of below 90%. Their median lowest nocturnal SaO₂ was 84.0 (range 70.93)% and their mean oxygen saturation in the course of desaturation episodes (Mmin SaO2) was 86.4 (range 83.6–91.5)%. An increased mean V_A/Q ratio of ventilation distribution was associated with a reduced DL_co Increased nocturnal episodes of wakefulness and of stage I sleep correlated with increased dead space ventilation and dispersion of the ventilation distribution. Patients with deep nocturnal desaturations had a low mean V_A/Q ratio of the perfusion distribution (Q mean) (r=0.87, P<0.01) and increased perfusion of inferior V_A/Q areas (0.1 V_A/Q<0.3). Low Mmin SaO₂ was associated with low morning PaO₂ and a low Q mean. COLD patients with solely nocturnal hypoxaemia have a high degree of pulmonary hyperinflation and emphysema. Increased sleep disruption is associated with more severe small airway disease. Increased perfusion of sparsely ventilated areas is associated with more pronounced nocturnal desaturations.     

Influence of long‐term oxygen therapy on heart rate and QT time‐series in hypoxic patients with chronic obstructive pulmonary disease

Background: There is increasing interest in the cardiovascular pathology independently associated with chronic obstructive pulmonary disease (COPD). We examined the influence of long‐term oxygen therapy (LTOT) on heart rate (RR) and QT time‐series in COPD. Methods: Ten hypoxic stable COPD patients underwent Holter ECG monitoring for 24 h and physical activity/energy expenditure monitoring for 5 days before and after LTOT. Variability of RR and QT time‐series was quantified using standard statistics and their structural (correlation/scaling) properties were assessed using multifractal analysis. Pre‐ and post‐LTOT cardiac/activity parameters were compared to examine the influence of oxygen therapy and circadian variation. Results: PaO₂ increased (P = 0·0004) whilst PaCO₂ was unchanged (P = 0·56) following LTOT. Activity/energy expenditure estimates were also unchanged following LTOT (P = 0·64–0·99), but RR variability was increased during the morning (P < 0·05) and night (P < 0·1, trend only). Multifractality of RR and QT time‐series was not significantly changed following LTOT, although QT multifractality showed some time‐dependent fluctuations. Trends in RR and QT time‐series over 24‐h were similar pre‐ and post‐LTOT, indicating a generally normal circadian response. Conclusions: An increase in HRV following LTOT (but notably in the absence of altered activity levels) provides tentative evidence that LTOT has a direct effect on heart rate control in COPD. This beneficial influence was expressed mainly during the morning, and the relevance of this diurnal variation in response requires further investigation. It was also confirmed that both RR and (to a lesser degree) QT time‐series in COPD have a multifractal structure, and this is not affected appreciably by LTOT.     

Regional V˙A/Q˙ ratios in man using 133Xe and single photon emission computed tomography (SPECT) corrected for attenuation

We describe a technique to obtain non-invasively regional pulmonary ventilation–perfusion ratios (V˙_A/Q˙) using single photon emission computed tomography (SPECT) and continuous infusion of ¹³³Xe. Single photon transmission tomography was used for attenuation correction, for delineation of the lungs and for V˙_A/Q˙ calculations. Data are presented for six normal subjects and compared to those for two patients with moderate chronic obstructive pulmonary disease (COPD). The mean V˙_A/Q˙ for the whole lung of the normal subjects ranged from 0·49 to 0·65, group mean 0·56 ± 0·07 (1 SD), and there was no significant difference between the right and left lung. The consistently too low V˙_A/Q˙ values are related to the inability to measure regional blood volume and the low resolution of the scintillation camera, giving an under-estimation of tracer input. For the normal subjects, the dispersion of V˙_A/Q˙, as defined by the standard deviation of the individual distribution functions, ranged from 0·12 to 0·19. One of the patients was characterized by a low mean V˙_A/Q˙ of 0·35, and the other patient had a wide dispersion (SD) of V˙_A/Q˙ of 0·37. In the normal subjects, a consistent V˙_A/Q˙ gradient was found only in the ventrodorsal direction. ¹³³Xe and SPECT can be used to obtain meaningful biological information regarding ventilation/perfusion relationships of potential clinical value.     

Potassium and ventilation during positive and negative work inpatients with chronic obstructive pulmonary disease

In patients with chronic obstructive pulmonary disease (COPD),reduced ventilatory reserves limit exercise tolerance. In these patients, the ventilatoryrequirements of eccentric exercise (negative work, W_neg) are lower thanthose of concentric exercise (positive work, W_pos) at similar workloads.In this study, we investigated the relationship between plasma potassium levels and ventilationduring W_pos and W_neg in these patients. Twelvepatients with stable COPD [mean (SD) FEV₁ 46% (16) of predicted]performed W_pos and W_neg on a cycle ergometer(6 min of exercise; interval ≥1 h) in a randomized order at a constant workload of50% of the individual maximum (positive) work capacity. Minute ventilation (V_E) and arterial plasma potassium concentration ([K⁺]_a) were measured at rest, and at 1-min intervals during exercise and during 3 min ofrecovery. V_E increased less during W_neg thanduring W_pos [6 (range 3–26) vs. 18 (range 8–28) l min^?1; P<0·01]. V_E during W_neg was reduced in proportion to VCO ₂.The increase in [K⁺]_a during W_pos and W_neg [0·45 (range 0·26–0·75) and0·34 (range 0·1–0·97) mM ] did not differsignificantly. V_E was closely correlated with VCO ₂ during both types of exercise. V_E was also closelycorrelated with [K⁺]_a, but the slope of the relationship between[K⁺]_a and V_E was steeper during W_pos than during W_neg [39·1 (range15·2–88·6) vs. 18·3 (range7·2–37·3) l min^?1 mM ^?1; P=0·012]. In contrast, the slope of the relationship betweenVCO ₂ and V_E was similar during bothtypes of exercise [27?8 (range 19·2–37·1) vs. 32·1 (range19·8–48·4)]. Thus, for a given increase in [K⁺]_a, the increase in V_E was significantly less during W_neg. In patients with COPD, potassium did not explain the difference inexercise ventilation between W_neg and W_pos, andmay not play a significant role in the control of breathing during low-intensity exercise.     

Pulmonary capillary blood flow by partial CO2 rebreathing: importance of the regularity of the respiratory pattern

The partial CO₂ rebreathing technique has been shown to be a reliable non‐invasive method for measurement of pulmonary capillary blood flow (Q˙_c), but experience with this technique has been limited to controlled mechanical ventilation. In this study, we evaluated this technique during spontaneous and oriented ventilation in nine subjects without known cardiopulmonary disease. Subjects underwent 10 consecutive (Q˙_c) measurements with both spontaneous and oriented ventilation. Breath‐by‐breath gas exchange was measured and (Q˙_c) was calculated from changes in CO₂ elimination and P_ETCO₂, which were achieved by sudden increase of the apparatus deadspace (rebreathing period). An exponential curve was fitted to the P_ETCO₂ values in the rebreathing period in order to estimate P_ETCO₂ at equilibrium. We found that mean (Q˙_c) values were not influenced by the ventilation pattern (P=0·51), but that the intra‐individual variability with oriented ventilation (median=16·0%) was significantly lower than with spontaneous ventilation (median=31·8%, P=0·039). Accordingly, the curve fitting for rebreathing P_ETCO₂ rise failed in 4·4% of measurements with oriented ventilation vs. 18·9% of measurements with spontaneous ventilation (P=0·039). Our results suggest that the performance of the partial CO₂ rebreathing technique is adversely affected by spontaneous ventilation and, consequently, that this method should be reserved for patients with regular respiratory patterns.     

Excessive exercise ventilation in moderate left heart dysfunction. Influence of postural changes in central haemodynamics and blood gases

To evaluate the relative importance of pulmonary congestion and peripheral hypoxia as causes for the excessive exercise ventilation in left heart dysfunction, seven patients with excessive ventilation and distinct left heart dysfunction during moderate exercise (LHD), and seven control patients with essentially normal exertional functions (CTR), had ventilation, central haemodynamics, arterial and mixed venous blood gases examined at rest and exercise, 32 W (25–40) in the LHD group and 44 W (33–49) in the CTR group, in lying and sitting positions. Change from lying to sitting exercise, led to fall in pulmonary artery wedge pressure (PAWP) from 31·0 ± 5·5 to 8·8 ± 5·0 mmHg in the LHD group, compared with from 13·7 ± 1·0 to 2·1 ± 2·4 mmHg in the controls, while ventilation/O₂ intake ratio (V˙/V˙O₂) and physiological dead space/tidal volume ratio (V_D/V_T) showed a tendency to rise, from 36·3 ± 8·8 to 39·2 ± 7·4, and from 0·35 ± 0·11 to 0·39 ± 0·09, respectively, in the LHD group, and from 27·5 ± 3·1 to 28·7 ± 5·3, and from 0·19 ± 0·09 to 0·21 ± 0·12 in the controls. Mixed venous O₂ tension (PvO ₂) showed a marked decline from 3·60 ± 0·33 to 3·26 ± 0·36 kPa in the LHD group, as compared with from 3·94 ± 0·28 to 3·71 ± 0·29 kPa in the controls, while the calculated physiologic shunt (Q˙_s/Q˙_t) suggested improved alveolo‐arterial gas exchange. The data fit in with recent studies ascribing the excessive exercise ventilation to a combination of signals from hypoxia‐induced changes, particularly in the exercising muscles, and augmented ergoreflex and central and peripheral chemoreceptor activity, partly to changes in the integrated control of ventilation and circulation, not to mechanisms related to pulmonary congestion.     

Metabolic cost of locomotion during treadmill walking with blood flow restriction

We explored whether interval walking with blood flow restriction (BFR) increases net metabolic cost of locomotion in healthy young men at their optimal walking speed. We also determined whether decreased walking economy resulting from BFR might be accompanied by an increase in ventilation relative to VO₂ and VCO₂. Finally, we examined possible relationships between the changes in ratings of perceived exertion (RPE) and those obtained in minute ventilation (V_E) during walking with BFR. Eighteen healthy men (age: 22·5 ± 3·4 years) performed graded treadmill exercise to assess VO_2max. In a randomized fashion, participants also performed five bouts of 3‐min treadmill exercise with and without BFR at their optimal walking speed. Walking with BFR elicited an overall increase in net VO₂ (10·4%) compared with that seen in the non‐BFR condition (P<0·05). The participants also demonstrated greater V_E and V_E/VO₂ values while walking with BFR (P<0·05). Conversely, V_E/VCO₂ was similar between conditions at each walking bout. We found no significant correlation between the changes in V_E and RPE induced by walking with BFR (r = 0·38, P>0·05). Our results indicate that (i) BFR decreases net walking economy in healthy young men, even at their optimal walking speed; (ii) heightened ventilatory drive may explain a small proportion of BFR effects on walking economy; and (iii) the ventilatory responses to BFR walking may be largely independent of changes in perceived exertion and are likely matched to the flux of CO₂ between muscles and respiratory centres.     

Acute effects of continuous rotational therapy on ventilation-perfusion inequality in lung injury

Objective: To investigate ventilation-perfusion (V_A/Q) relationships, during continuous axial rotation and in the supine position, in patients with acute lung injury (ALI) using the multiple inert gas elimination technique. Design: Prospective investigation. Setting: Eighteen-bed intensive care unit in a university hospital. Patients and interventions: Ten patients with ALI (PaO₂/FIO₂ ratio < 300 mm Hg) were mechanically ventilated in a pressure controlled mode and placed on a kinetic treatment table. Measurements and results: Distributions of V_A/Q were determined 1) during rotation (after a period of 20 min) and 2) after a resting period of 20 min in the supine position. During axial rotation, intrapulmonary shunt (19.1 ± 15 % of cardiac output) was significantly reduced in comparison with when in the supine position (23 ± 14 %, p < 0.05), areas with “low” V_A/Q were not affected by the positioning maneuver. General V_A/Q mismatch (logarithmic distribution of pulmonary blood flow) was decreased during rotation (0.87 ± 0.37) in comparison with when the patient was in the supine position (0.93 ± 0.37, p < 0.05). Arterial oxygenation was significantly improved during continuous rotation (PaO₂/FIO₂ = 217 ± 137 mm Hg) as compared with in the supine position (PaO₂/FIO₂ = 174 ± 82 mm Hg, p < 0.05). The positive response of the continuous rotation on arterial oxygenation was only demonstrated in patients with a Murray Score of 2.5 or less, indicating a “mild to moderate” lung injury, while in patients presenting with progressive ARDS (Murray Score > 2.5), the acute positive response was limited. Conclusions: Continuous axial rotation might be a method for an acute reduction of V_A/Q mismatch in patients with mild to moderate ALI, but this technique is not effective in late or progressive ARDS. Further studies including a large data collection are needed. Received: 19 June 1997 Accepted: 6 November 1997     

Comparison between ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia in healthy sleeping man

Summary. Ventilatory and mouth occlusion pressure (P_0·1) responses to progressive isocapnic-hypoxia and hyperoxic-hypercapnia were compared in eleven healthy sleeping men during the same night. Hypoxic and hypercapnic responses were determined during wakefulness, non-rapid and rapid-eye-movement sleep. The following parameters were measured: minute ventilation (V?E), tidal volume (V_T), ‘duty cycle’ (T_l/T_T), mean inspiratory flow rate (V_T/T_l) and P_0·1, an index of the neuromuscular inspiratory drive. To allow a direct comparison between the two types of chemostimuli, responses were characterized by the value of the different parameters at ‘equivalent’ levels of hypoxia and hypercapnia, i.e., at levels which produced the same P_0·1 during wakefulness: an oxyhaemoglobin saturation (Sao₂) of 94% during the isocapnic-hypoxic tests (P_ETco₂=42·5±1·2 mmHg) was found to be equivalent to a P_etco₂ of 47·4±3·7 mmHg during hypoxic-hypercapnic tests. For both tests, the arousal levels of the stimulus and of P_0·1 were similar in all sleep stages. Sleep did not significantly modify P_0·1 or breathing pattern responses to hypoxia (Sao₂=94%). In contrast, at the ‘equivalent’ level of hypercapnic stimulation, P_0·1 (P<0·05) and V?_E (P<0·01) responses were significantly impaired, particularly in REM sleep, with a decrease in V_T (P<0·01) and V_T/T_l (P<0·05) responses. The results suggest that CO₂ intracranial receptor mechanisms are more affected by sleep than the O₂ peripheral receptor activity.     

Transcutaneous Pco2 and Po2: A multicenter study of accuracy

A multicentcr study used 756 samples from 251 patients in 12 institutions to compare arterial (PaO₂, PaCO₂) with transcutaneous (PsO₂, PsCO₂) oxygen and carbon dioxide tensions, measured usually at 44°C. Of these samples, 336 were obtained from 116 neonates, 27 from 25 children with cystic fibrosis, and 140 from 40 patients under general anesthesia. Ninety-one patients were between 4 weeks and 18 years of age, 32 were between 18 and 60 years, and 12 were over 60. The ratio of transcutaneous to arterial P(s/a)CO₂ was 1.01 ±0.11 with PaCO₂ less than 30 mm Hg, increasing to 1.04 ±0.08 at PaCO₂ greater than 40 mm Hg. Mean bias and its standard deviation (PsCO₂ — PaCO₂) were + 1.3 ± 3.9 mm Hg in the entire group, + 1.8 ± 4.2 mm Hg in neonates (NS). Bias was +0.2 ± 2.7 mm Hg when PaCO₂ was less than 30 mm Hg (N = 175, NS), 1.0 ± 3.4 with 30 < PaCO₂ < 40 (n = 329,p < 0.001), and +2.04 ± 4.00 mm Hg with 40 < PaCO₂ < 70 (n = 229,p < 0.001). These data suggest that, using transcutaneous PCO₂ monitors with inbuilt temperature correction of 4.5%/‡C, the skin metabolic offset should be set to 6 mm Hg. The linear regression was PsCO₂ =1.052(PaCO₂)-0.56, Sy·x = 3.92, R = 0.929 (n = 756); and PsCO₂ = 1.09(PaCO₂)-1.57, Sy·x = 4.17, R = 0.928 in neonates (n = 336). The use of vasopressors and vasodilators had no significant effect on bias or its standard deviation or on regression slope and intercept (n = 78). In cystic fibrosis patients, bias and standard deviation were 0.0 ± 1.7 mm Hg (n = 27). Under anesthesia, PsCO₂ = 1.07PaCO₂-1.58, with bias and standard deviation = 0.6 ± 3.5 (n = 140). For oxygen, at PaO₂ ≤ 80 the ratio P(s/a)O₂ = 1.05 ± 0.16 in nconates and 0.93 ± 0.21 in older patients, but when PaO₂ > 80, P(s/a)O₂ fell to 0.88 ± 0.18 in neonates and 0.74 ± 0.21 in older patients. The errors were significantly greater (p < 0.001) in older patients than in neonates above but not below 80 mm Hg, and within both groups errors were significantly greater above than below 80 mm Hg.     

Influence of alveolar ventilation changes on calculated gastric intramucosal pH and gastric-arterial PCO2 difference

Objective: To evaluate the influence of changes in alveolar ventilation on the following tonometry-derived variables: gastric intramucosal CO₂ tension (PtCO₂), gastric arterial CO₂ tension difference (P_gapCO₂), gastric intramucosal pH (pHi) and arterial pH-pHi difference (pH_gap). Design: Clinical prospective study. Setting: A medical intensive care unit in a university hospital. Patients: Ten critically ill, mechanically ventilated patients requiring hemodynamic monitoring with pulmonary artery catheter. Interventions: Gastric tonometer placement. A progressive increase in tidal volume (V_T) from 7 to 10 ml/kg followed by an abrupt return to baseline V_T level. Measurements and main results: Tonometer saline PtCO₂ and hemodynamic data were collected hourly at various V_T levels: H0 and H0' (baseline V_T = 7 ml/kg), H1 (V_T = 8 ml/kg), H2 (V_T = 9 ml/kg), H3 (V_T = 10 ml/kg), H4 (baseline V_T). During the “hyperventilation phase” (H0-H3), pHi (p < 0.01) and pH_gap (p < 0.05) increased but P_gapCO₂ remained unchanged. Cardiac output (CO) was not affected by ventilatory change. During the “hypoventilation phase” (H3-H4), pHi fell from 7.27 ± 0.11 to 7.23 ± 0.09 (p < 0.01) and P_gapCO₂ decreased from 16 ± 5 mmHg to 13 ± 4 mmHg (p < 0.05). V_T reduction was associated with a significant cardiac output elevation (p < 0.05). Conclusions: PaCO₂ and PtCO₂ are similarly influenced by the changes in alveolar ventilation. Unlike pHi, the P_gapCO₂ is not affected by ventilation variations unless CO changes are associated. Received: 15 June 1998 Final revision received: 21 October 1998 Accepted: 16 November 1998     

Aspiration of dead space allows normocapnic ventilation at low tidal volumes in man

Objective: Aspiration of dead space (ASPIDS) improves carbon dioxide (CO₂) elimination by replacing dead space air rich in CO₂ with fresh gas during expiration. The hypothesis was that ASPIDS allows normocapnia to be maintained at low tidal volumes (V_T). Design: Prospective study. Setting: Adult intensive care unit in a university hospital. Patients: Seven patients ventilated for neurological reasons were studied. All patients were clinically and haemodynamically stable and monitored according to clinical needs. Interventions: ASPIDS implies that, during expiration, gas is aspirated through a catheter inserted in the tracheal tube. Simultaneously, a compensatory flow of fresh gas is injected into the inspiratory line. ASPIDS was achieved with a computer/ventilator system controlling two solenoid valves for aspiration and injection. Results: At the basal respiratory rate of 12.6 breaths min^–1, with ASPIDS V_T decreased from 602 to 456 ml, as did the airway pressures to a corresponding degree. PaCO₂ and PaO₂ remained stable. At a frequency of 20 breaths min^–1, with ASPIDS V_T was further reduced to 305 ml with preserved normocapnia. ASPIDS did not interfere with the positive end-expiratory pressure (PEEP) level. No intrinsic PEEP developed. All patients remained stable. No haemodynamic or other side effects of ASPIDS were noticed. Conclusion: The results of this study suggest that ASPIDS may be a useful and safe modality of mechanical ventilation that limits alveolar pressure and minute ventilation requirements while keeping PaCO₂ constant. Received: 21 December 1998 Final revision received: 28 April 1999 Accepted: 3 May 1999     

Multiple breath nitrogen dead space

Summary. Ventilatory efficiency for eliminating CO₂ is expressed by the physiological dead space, V_Dphys = (1-PE CO₂/Pa CO₂) ×V_T, where PE is the mixed exhaled and Pa the arterial CO₂-tension and V_T the tidal volume. We used data from the multiple breath N₂-wash-out with oxygen for calculating a functional dead space for nitrogen. V_DFN₂= (1 -FEN₂/FEN₂/FidN₂) ×V_T. F_EN₂ is the mixed exhaled N₂-fraction and FidN₂ the calculated mean alveolar N₂-fraction during a wash-out with the same number of breaths to reach 2% N₂ in end tidal air, but having completely even distribution. FidN₂ is shown to be 0·20±0·01 for wash-outs using 20–150 breaths. The method was applied to wash-outs from 21 healthy volunteers, 18 patients with chronic obstructive lung disease and two subjects with acute bronchospasm. V_DF was well related to V_D phys CO₂ (r= 0·78) but higher than the latter. In subjects with lung disease V_DF was inversely related to the degree of obstruction expressed by forced expiratory volume in one second per cent of vital capacity (r= 0·85). The subjects with bronchospasm had very high V_D/V_TMF, in relation to their FEV%. If airway dead space predicted from height and sex is subtracted from V_DF, the resulting alveolar dead space will be a good expression for uneven gas distribution in the lungs. We also deduced a direct mathematical relation between lung clearance index and V_D/V_TF. The documented good reproducibility of LCI is thus also valid for V_D/V_TF, while the latter better expresses ventilatory efficiency.     

Evaluation of a modified acetylene rebreathing method for the determination of cardiac output

Summary. In order to evaluate a computerized modified acetylene rebreathing method for the determination of cardiac output, 15 healthy subjects were studied at different levels of their maximal oxygen uptake (V?o_2max). Submaximal exercise was performed on a cycle ergometer and maximal exercise on a treadmill. Oxygen uptake, heart rate, and cardiac output (acetylene method) were determined in all test situations. In seven subjects simultaneous determinations of cardiac output were made by a modified acetylene rebreathing method (Q?_A) and a dye dilution method (Q?_D) Furthermore, a new resting rebreathing technique was used. The methodological error for (Q?_A)(means of double samples) was 0·37 litre min^-1 (2·8%) in the same individual at 150 W. The corresponding values between individuals were 0·71 (rest), 0·41 (50 W), 0·69 (150 W), and 0·40 litre min^-1 (V?o_2max). Thus the methodological error of the modified acetylene method was very low. There was a significant difference (P<0·01), however, between the acetylene method and the dye dilution method, which showed a lower value for Q?_A at all levels. This was probably due to the long response time of the mass spectrometer combined with anatomical and physiological arteriovenous shunt effects in the lungs during exercise. When these factors were considered the correcting formula was:Q?_Ac=Q?_A+0·005·Q²_A There was no significant difference between the corrected cardiac output values (Q?_Ac) and the corresponding Q?_D values. In conclusion, this modified acetylene rebreathing method is a very useful non-invasive method for measuring cardiac output at rest as well as during heavy exercise.     

Anticipating maximal or submaximal exercise: no differences in cardiopulmonary responses

Background: Anticipation before the start of exercise may influence the cardiopulmonary responses during exercise. If anticipation influences the responses differently with maximal and submaximal exercises, normative values for submaximal responses will not be comparable unless exercise has been continued to the same end point. Methods: Twelve healthy subjects (five men) aged 18–27 years had a maximal exercise test and a submaximal exercise test on a cycle ergometer on different days and in random order. They were not aware of the specific purpose of the study and were informed 15 min before the tests whether it should be maximal or submaximal. Workload increased with 15 W min^?1 until exhaustion or to 80% of predicted maximal heart rate (HR). HR, oxygen uptake (VO₂), carbon dioxide production (VCO₂), minute ventilation (V_E) and tidal volume (V_T) were averaged over 20 s intervals. Linear regression of the HR–VO₂ relationship and quadratic regression of the V_T–V_E relationship were performed for each individual, and the regression coefficients for maximal and submaximal tests were compared. Results: The regression models described the V_T–V_E responses with a R² > 0·85 in 23 of 24 tests, and the HR‐VO₂ responses with a R² > 0·90 in all tests. The regression coefficients of the relationships were not significantly different with maximal and submaximal exercises. Conclusion: Anticipation appears not to influence the responses to progressive maximal and submaximal exercise tests with the same rate of increase in load. Normative values at submaximal exercise levels are not influenced by the targeted end point of exercise.     

Reduction of ventilator settings allowed by intravenous oxygenator (IVOX) in ARDS patients

Objective To evaluate the possibility of reducing ventilator settings to “safe” levels by extrapulmonary gas exchange with IVOX in ARDS patients. Design Uncontrolled open clinical study. Setting Medical Intensive Care Unit of a University Hospital. Patients 6 patients with ARDS who entered into IVOX phase II clinical trials. Interventions The end-point of this study was to reduce ventilator settings from the initial values, recorded on the day of inclusion, to the following: peak inspiratory pressure <40 cmH₂O, mean airway pressure <25 cmH₂O and tidal volume <10 ml/kg. Trials to achieve this goal were made on volume-controlled ventilation within the 24h before and after IVOX insertion. Comparison of the results achieved during these trials used wilcoxon test. Results Before IVOX implantation reduction of ventilator settings was not possible in the 6 patients, despite a non-significant increase in PaO₂/FIO₂ was achieved. IVOX permitted significant decrease in PaCO₂ (from 60.5±15 to 52±11 mmHg;p=0.02) before any modification of the ventilatory mode. After IVOX insertion, a significant decrease of the ventilator settings was performed: peak and mean airway pressures dropped from 44±10 to 36.8±6.7;p=0.02 and from 26.3±5.6 to 22.5±3.9 cmH₂O;p=0.02, respectively. Concommitantly, PaCO₂ remained unchanged and PaO₂/FIO₂ increased significantly from 93±28 to 117±52;p=0.04. The interruption of oxygen flow on IVOX was associated with a slight decrease of the oxygen variables. Tolerance of IVOX was satisfactory. However, a significant decrease both in cardiac index and in pulmonary wedge pressures (from 4.5±1.2 to 3.4±9;p=0.03 and from 16±5 to 11±2;p=0.04, respectively) was observed. Conclusion Gas exchange achieved by IVOX allowed reduction of ventilator settings in 6 ARDS patients in whom previous attempts have failed. CO₂ removal by the device, may explain these results. Efficacy of IVOX on arterial oxygenation was uncertain.     

Ventilatory response to CO2 in patients with snoring,obstructivehypopnoea and obstructive apnoea

Obstructive sleep apnoea (OSA) is caused by an obstruction of the upper airway. Sufficientsensitivity to CO₂ in the respiratory centre is known to be a critical factor for adequatetone in the upper airway muscles. The hypothesis of this study is, therefore, that the ventilatoryresponse to CO₂ is reduced in patients with OSA. Twenty-six patients who sufferedfrom snoring, 19 snoring patients with obstructive hypopnoea (OH) and 33 snoring patients withobstructive apnoea (OA), were studied. The control group consisted of 25 subjects from a randomsample with no history of snoring or daytime sleepiness. Tests of the hyperoxic and hypoxicventilatory response to CO₂ were performed, as well as static and dynamic spirometry.Subjects in the OA group displayed a higher hyperoxic (E_E/F_etCO _2hy=12·6 l min^?1/%) and hypoxic (E_E/F_etCO _2ho=15·7 l min^?1/%) ventilatory responseto CO₂ than patients with obstructive hypopnoea(E_E/F_etCO_2hy=8middot;6 l min^?1/%; E_E/F_etCO _2ho=15·2 l min^?1/%), snorers(E_E/F_etCO _2hy=8·4 l min^?1/%;E_E/F_etCO _2ho=12·7 l min^?1/%) and non-snorers(E_E /F_etCO _2hy=7·6 l min^?1/%;E_E/F_etCO _ho=9·6 l min^?1/%). Multiple regression analysis revealsthat neck circumference, apnoea index, oxygen desaturation index, PCO ₂ and sex (male gender) are correlated with E_E/F_etCO _2hy (R²=0·43).Multiple regression analysis also reveals that ERV (expiratory reserve volume) and sex (malegender) are correlated with E_E/F_etCO _2ho ((R²=0·21). Arguing against thehypothesis, patients with OSA displayed an increased hyperoxic and hypoxic ventilatory responseto CO₂ . Nocturnal apnoea frequency and the obesity factor in OSA may havecontributed to these results.     

High frequency jet ventilation (HFJV) has no better haemodynamic tolerance than controlled mechanical ventilation (CMV) in cardiogenic shock

Six patients with acute myocardial infarction (AMI) complicated by cardiogenic shock were studied in order to compare the haemodynamic tolerance of controlled mechanical ventilation (CMV) and high frequency jet ventilation (HFJV). The comparative analysis of the two techniques was performed with the same levels of PaO₂ (CMV: 101±13 mmHg; HFJV: 104.2±14 p=ns); and PaCO₂ (CMV: 37±1.7; HFJV: 35.7±1.4p=ns). In this situation the values of mean airway pressure (Paw) did not differ significantly (CMV: 13±3 cm H₂O; HFJV: 12.6±3.8 cm H₂O) and no statistically significant difference in haemodynamic values was observed. These results demonstrate that in patients with cardiogenic shock, there is no difference between HFJV and CMV in terms of haemodynamic tolerance. Because of the more difficult clinical management of HFJV, this technique does not seem indicated as ventilatory support in patients with cardiogenic shock states. Presented in part as a communication to the Third Congress of the European Society of Intensive Care Medicine (Hamburg 1986).     

The effect of induced hypothermia on respiratory parameters in mechanically ventilated patients

Aim

Mild hypothermia is increasingly applied in the intensive care unit. Knowledge on the effects of hypothermia on respiratory parameters during mechanical ventilation is limited. In this retrospective study, we describe the effect of hypothermia on gas exchange in patients cooled for 24 h after a cardiac arrest.

Methods

Respiratory parameters were derived from electronic patient files from 65 patients at the start and end of the hypothermic phase and at every centigrade increase in body temperature until normo-temperature, including tidal volume, positive end expiratory pressure (PEEP), plateau pressure, respiratory rate, exhaled CO₂ concentrations (etCO₂) and FIO₂. Static compliance was calculated as V_T/P_plateau − PEEP. Dead space ventilation was calculated as (PaCO₂ − etCO₂)/PaCO₂.

Results

During hypothermia, PaCO₂ decreased, at unchanged PaCO₂-etCO₂ gap and minute ventilation. During rewarming, PaCO₂ did not change, while etCO₂ increased at unchanged minute ventilation. Dead space ventilation did not change during hypothermia, but lowered during rewarming. During hypothermia, PaO₂/FIO₂ ratio increased at unchanged PEEP levels. Respiratory static compliance did not change during hypothermia, nor during rewarming.

Conclusion

Hypothermia possibly improves oxygenation and ventilation in mechanically ventilated patients. Results may accord with the hypothesis that reducing metabolism with applied hypothermia may be beneficial in patients with acute lung injury, in whom low minute ventilation results in severe hypercapnia.     

Acute myocardial infarction with normal coronary arteries during septic shock from Neisseria meningitidis

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (?^·V_A/?^·Q) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and?^·V_A/?^·Qdistributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal?^·V_A/?^·Qratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal?^·V_A/?^·Qrelationships.