Hypercapnic Group Research Articles

Effects of Acetazolamide and Furosemide on Ventilation and Cerebral Blood Volume in Normocapnic and Hypercapnic Patients With COPD

Effects of chronic metabolic alkalosis and acidosis and their relation to central chemoregulation may differ between normocapnic and chronic hypercapnic patients with COPD. The relationship between responses of inspired ventilation (VI), mouth occlusion pressure (P(0.1)), and cerebral blood volume (CBV), to short-term changes in arterial PCO(2) was measured. Seventeen patients with chronic hypercapnia and COPD (PaCO(2) > 6.0 kPa) and 16 normocapnic patients with COPD (PaCO(2) < or = 6.0 kPa) [FEV(1) 27% predicted] were studied under baseline metabolic conditions and after 1 week of treatment with oral furosemide, 40 mg/d, or acetazolamide, 500 mg/d. Hypercapnia (change in end-tidal carbon dioxide > 1 kPa) was induced by administering adequate amounts of carbon dioxide in the inspired air. CBV was measured using near-infrared spectroscopy. Compared with baseline metabolic condition, chronic metabolic acidosis and alkalosis did not change ventilatory (Delta VI/Delta PaCO(2)) and cerebrovascular (Delta CBV/Delta PaCO(2)) reactivity. Base excess (BE) decreased by 6.8 +/- 1.1 mEq/L and 6.9 +/- 1.6 mEq/L, respectively, in the normocapnic and chronic hypercapnic COPD groups during metabolic acidosis, resulting in a not-quite-significant leftward shift of both the ventilatory and cerebrovascular carbon dioxide response curve. BE increased by 2.3 +/- 1.2 mEq/L and 1.2 +/- 1.3 mEq/L, respectively, during chronic metabolic alkalosis in both COPD groups, without concomitant shift. Poor correlations between ventilatory and cerebrovascular carbon dioxide responsiveness (Delta CBV/Delta PaCO(2) and Delta VI/Delta PaCO(2), Delta CBV/Delta PaCO(2) and Delta P(0.1)/Delta PaCO(2), respectively) were found irrespective of baseline, respiratory condition, and induced metabolic state. Normocapnic and chronic hypercapnic COPD patients have the same ventilatory and cerebrovascular carbon dioxide responsiveness irrespective of induced metabolic state.

Long-term effects of treatment with nasal continuous positive airway pressure on lung function in patients with overlap syndrome.

We assessed the effects of chronic nasal continuous positive airway pressure (CPAP) therapy on lung function in a series of unselected patients with overlap syndrome, and we determined whether there were differences in the response induced by CPAP between hypercapnic (PaCO2 > or =45 mm Hg) and eucapnic patients with overlap syndrome. The study population included 55 unselected patients (48 men, mean age of 58.5 +/- 10.5 years) with a concurrent diagnosis of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea-hypopnea syndrome (OSAHS) who had been referred to the Department of Pulmonology of our hospital over 2 consecutive years and in whom work-up studies resulted in the prescription of nasal CPAP therapy. An apnea-hypopnea index (AHI) greater than or equal to 10 in the cardiorespiratory polygraphy was required for the diagnosis of OSAHS. A forced expiratory volume in one second (FEV1) less than 80% and FEV1-forced vital capacity (FVC) ratio less than 70% of the reference values were required for the diagnosis of COPD. Control lung function studies and arterial blood gas measurements were performed at 6 and 18 months of CPAP therapy. These patients with overlap syndrome accounted for 28.5% of all patients with OSAHS treated with CPAP during the study period. The mean AHI was 37.3 +/- 26.1 and the mean CPAP level 7.3 +/- 1.3 cm H2O. Thirty-three patients were hypercapnic (PaCO2 > or = 45 mm Hg) and 22 eucapnic. The hypercapnic group had higher AHI value (44.3 +/- 26.9) than the eucapnic group (28.6 +/- 21.9) (P < 0.05). After 6 months of CPAP therapy, there were statistically significant increases in PaO2, FEV1, and FVC, accompanied by significant decreases in PaCO2, serum bicarbonate levels, and alveolar-arterial oxygen difference. Response of overlap syndrome patients to CPAP therapy was superior in the hypercapnic group, particularly in relation to improvement of arterial blood gases. However, statistically significant differences in all parameters for the comparison between 6 and 18 months were not recorded.

The Effects of Normocapnia and Hypercapnia on Venous Oxygen Saturation and Lactate Levels at the Jugular Bulb during Rewarming from Hypothermic Cardiopulmonary Bypass

Background: Neurologic and neuropsychologic dysfunction after cardiopulmonary bypass is frequent and can be caused by inadequate cerebral perfusion and oxygenation. A decrease of suggests a situation in which the oxygen supply to the brain is insufficient to meet metabolic demands. This study investigated the effects of normocapnia and hypercapnia on changes in and lactate levels during rewarming from hypothermic cardiopulmonary bypass. Methods: Anesthesia was induced and maintained with bolus and continuous infusion of fentanyl, midazolam and vecuronium. Patients were assigned to a normocapnic (: 35-40 mmHg, n = 10) or hypercapnic (: 45-50 mmHg, n = 10) group during rewarming. and lactate levels at the jugular bulb were measured at 30, 34 and 37 nasopharyngeal temperature. Results: There was not a reduction in to than the normocapnic group at 30, 34 and 37 nasopharyngeal temperature during rewarming (P than normocapnia and may contribute to the prevention of postoperative neurologic dysfunction, especially in patients having a low .

Bone loss in patients with untreated chronic obstructive pulmonary disease is mediated by an increase in bone resorption associated with hypercapnia.

This study sought to determine whether the bone loss in untreated chronic obstructive pulmonary disease (COPD) is associated with hypercapnia and/or respiratory acidosis. Bone mineral density (BMD) measured at the distal forearm of the nondominant arm (with peripheral quantitative computed tomography [pQCT]) and serum markers of bone turnover were determined in 71 male patients with untreated COPD and 40 healthy male subjects who matched the patients in age, weight, and body mass index (BMI). The COPD patients, compared with controls, had reduced pulmonary functions, lower arterial pH, and elevated arterial partial pressure of CO2 (PCO2) The BMD (in T score) was significantly lower in COPD patients than that in control subjects (-1.628 +/- 0.168 vs. -0.058 +/- 0.157; p < 0.001). The BMD of COPD patients correlated positively with arterial pH (r = 0.582; p < 0.001), negatively with PCO2 (r = -0.442; p < 0.001), and negatively with serum cross-linked telopeptide of type I collagen (ICTP), a bone resorption marker (r = -0.444; p < 0.001) but not with serum osteocalcin, a bone formation marker. Serum ICTP, but not osteocalcin, correlated with PCO2 (r = 0.593; p < 0.001) and arterial pH (r = -0.415; p < 0.001). To assess the role of hypercapnia, COPD patients were divided into the hypercapnic (PCO2 > 45 mm Hg; n = 35) and eucapnic (PCO2 = 35-45 mm Hg) group (n = 36). Patients with hypercapnia had lower BMD, lower arterial pH, and higher serum ICTP than did patients with eucapnia. Arterial pH and serum ICTP of eucapnic patients were not different from those of controls. To evaluate the role of uncompensated respiratory acidosis, COPD patients with hypercapnia were subdivided into those with compensatory respiratory acidosis (pH > or = 7.35; n = 20) and those with uncompensated respiratory acidosis (pH < 7.35; n = 15). The BMD and serum ICTP were not different among the two subgroups. In conclusion, this study presents the first associative evidence that the bone loss in COPD is at least in part attributed to an increased bone resorption that is associated primarily with hypercapnia rather than uncompensated respiratory acidosis.

Treatment Effects on Carbon Dioxide Retention in Patients With Obstructive Sleep Apnea-Hypopnea Syndrome

This study was designed to examine respiratory control in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), with or without CO(2) retention. We recruited 10 body mass index-matched, apnea-hypopnea index-matched, age-matched, and lung function-matched OSAHS patients, according to their awake PaCO(2). Five patients were hypercapnic (PaCO(2), > or = 45 mm Hg), and five patients were eucapnic. Hypoxic responses (the ratio of the change in minute ventilation [DeltaV(E)] to the change in arterial oxygen saturation [DeltaSaO(2)] and the ratio of the change in mouth occlusion pressure over the first 100 ms of inspiration against an occluded airway [DeltaP(0.1)] to DeltaSaO(2)) and hypercapnic responses (DeltaV(E)/DeltaPCO(2) ratio and DeltaP(0.1)/DeltaPCO(2) ratio) were tested during wakefulness before treatment in all 10 patients, and before and during treatment (at 2, 4, and 6 weeks) with pressure support in the hypercapnic group. Hypercapnic patients had lower mean (+/- SD) DeltaV(E)/DeltaSaO(2) ratio than eucapnic patients (-0.17 +/- 0.04 vs -0.34 +/- 0.04 L /min/%SaO(2), respectively), lower mean DeltaP(0.1)/DeltaSaO(2) ratio (-0.04 +/- 0.02 vs -0.14 +/- 0.03 cm H(2)O/%SaO(2), respectively), and lower DeltaP(0.1)/DeltaPCO(2) ratio (0.23 +/- 0.1 vs 0.49 +/- 0.1 cm H(2)O/mm Hg, respectively) [p < 0.05]. After receiving noninvasive ventilation treatment, the hypercapnic and hypoxic responses of the hypercapnic patients increased. At 4 to 6 weeks, values for both responses had increased to within the normal range and PaCO(2) had fallen to < 45 mm Hg, while weight was unchanged. Depressed chemoresponsiveness plays a role that is independent of obesity in the development of CO(2) retention in some OSAHS patients, and it may be a response to sleep-disordered breathing.

Cerebral blood flow and metabolism during and after prolonged hypercapnia in newborn lambs.

To study the effects of prolonged (6 hrs) hypercapnia on cerebral blood flow and cerebral metabolism in newborn lambs and to evaluate the effects on cerebral blood flow and cerebral metabolism on return to normocapnia after prolonged hypercapnia. Animal studies, using the newborn lamb, with comparison to control group. Newborn lambs of mixed breed, 1-7 days of age, were used for the study. Two groups of animals were studied: a hypercapnic group (n = 10) and a normocapnic control group (n = 5). Work was conducted in the research laboratories at Children's National Medical Center, Washington, DC. Animals were anesthetized with pentobarbital, intubated, paralyzed, and mechanically ventilated. After baseline measurements were made, CO2 was blended into the ventilator gas until a PaCO2 of 75-80 torr (10-10.6 kPa) was obtained. Measurements were made 1 hr after the desired PaCO2 was achieved and after 6 hrs of hypercapnia. After 6 hrs of hypercapnia, the ventilator gas was returned to the baseline value, that is, normocapnia. Measurements were made 30, 60, and 90 mins after PaCO2 returned to baseline. Six measurements were made during the study. For each measurement, blood samples were drawn from the sagittal sinus and brachiocephalic artery catheters and were analyzed for pH, hemoglobin concentration, oxygen saturation, and blood gas values. Cerebral blood flow (CBF) was measured by using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. Increasing PaCO2 from 37 +/- 3 torr to 78 +/- 6 torr (4.9 +/- 0.4 kPa to 10.3 +/- 0.8 kPa) for 1 hr increased CBF by 355%. After 6 hrs of PaCO2 at 78 +/- 3 torr (10.3 +/- 0.4 kPa), CBF remained 195% above baseline. At 30 mins of normocapnia, CBF had returned to baseline and remained at baseline until the conclusion of the study, a total of 90 mins of normocapnia. Cerebral oxygen consumption did not change during hypercapnia or with return to normocapnia. Oxygen transport increased 331% above baseline after 1 hr of hypercapnia and stayed 180% above baseline after 6 hrs of hypercapnia. Fractional oxygen extraction decreased by 55% at 1 hr of hypercapnia and stayed 39% below baseline at 6 hrs of hypercapnia. Healthy lambs seem to tolerate undergoing hypercapnia for 6 hrs with a return to normocapnia. The return to baseline of CBF and cerebral metabolism at normocapnia seen in our study with lambs may explain why prolonged hypercapnia appears to be well tolerated in mechanically ventilated patients. If these results can be extrapolated to human subjects, our study in lambs supports evidence that patients who have undergone permissive hypercapnia seem to be neurologically unaffected.

β-endorphin immunoreactivity during anaesthesia in equidae

To determine the effects of surgery, hypoxia, hypercapnia and flunixin administration on plasma β-endorphin immunoreactivity (BEI) in anaesthetized horses. Prospective crossover study. Six healthy adult Welsh Mountain ponies and seven healthy adult Thoroughbreds. Ponies were anaesthetized with thiopentone and halothane or with pentobarbitone and the horses with guaiphenesin, thiopentone and halothane. Ponies were anaesthetized for 2 hours and on separate occasions underwent a period of hypoxia, hypercapnia, anaesthesia only, or were given flunixin at induction. The horses were anaesthetized for 2 hours and on separate occasions underwent surgery to relocate one carotid artery subcutaneously or anaesthesia only. Plasma samples were taken pre-anaesthesia, at 20 minute intervals during, and after anaesthesia for BEI assay using radio-immunoassay. Analysis of variance of the concentration-time curve was used for statistical analysis. Pre-anaesthetic β-endorphin immunoreactivity (BEI) values ranged between 5.7 and 20.4 pmol L-1. Induction of anaesthesia caused a five to 10 fold increase in mean plasma BEI in all cases except the hypercapnia group. Halothane anaesthesia increased BEI in ponies and horses but there were no significant changes during pentobarbitone anaesthesia. The increase in BEI in the hypoxic group was greater (peak value 136.8 ± 32.2 pmol L-1) and sustained for a longer period compared with levels in those given halothane alone or in those which became hypercapnic. There was marked individual variation in the flunixin group and changes were not significant. Surgery in the horses resulted in the highest peak values in the study (182.5 ± 153.0 pmol L-1) but the AUC was not significantly higher than in the same animals without surgery, where the peak value was 102.9 ± 42.1 pmol L-1. CONCLUSIONS: Beta-endorphin appeared to be a sensitive marker of an endocrine stress response but its physiological role during equine anaesthesia is unknown. Unknown.

Severe head injuries: effects of pre-hospital mechanical ventilation on capnia

To assess the effect on PaCO2 of mechanical ventilation during prehospital management of severely head-injured patients. Retrospective observational study. Severely head-injured patients with Glasgow coma score < or = 8. All patients were sedated, with the trachea intubated and the lungs mechanically ventilated. According to the capnia measured at the admission in the neurosurgical intensive therapy unit they were allocated into one of the following three groups: hypocapnia group (PaCO2 < 30 mmHg), recommended capnia group (PaCO2 = 30-38 mmHg) and hypercapnia group (PaCO2 > 38 mmHg). Out of the 42 patients with similarly severe head injuries, 19% were included in the recommended capnia group (PaCO2: 34 +/- 2 mmHg), 38% in the hypocapnia group (PaCO2: 23 +/- 3 mmHg) and 43% in the hypercapnia group (PaCO2: 47 +/- 7 mmHg). In all except three, PaO2 was above 95 mmHg. The settings of ventilatory parameters on the ventilators were similar. In 81% of patients, mechanical ventilation was inadequate as far as PaCO2 levels are concerned. Major hypocapnia and hypercapnia carry a potential risk for cerebral ischaemic. Therefore it is recommended to monitor PETCO2 during prehospital transport in medical ambulances and to determine arterial blood gases at arrival of severely head-injured patients in the admission unit for emergencies.

Improvements in Lung Function, Exercise, and Quality of Life in Hypercapnic COPD Patients After Lung Volume Reduction Surgery

To determine the impact of preoperative resting hypercapnia on patient outcome after bilateral lung volume reduction surgery (LVRS). We prospectively examined morbidity, mortality, quality of life (QOL), and physiologic outcome, including spirometry, gas exchange, and exercise performance in 15 patients with severe emphysema and a resting PaCO2 of > 45 mm Hg (group 1), and compared the results with those from 31 patients with a PaCO2 of < 45 mm Hg (group 2). All preoperative physiologic and QOL indices were more impaired in the hypercapnic patients than in the eucapnic patients. The hypercapnic patients exhibited a lower preoperative FEV1, a lower diffusing capacity of the lung for carbon monoxide, a lower ratio of PaO2 to the fraction of inspired oxygen, a lower 6-min walk distance, and higher oxygen requirements. However, after surgery both groups exhibited improvements in FVC (group 1, p < 0.01; group 2, p < 0.001), FEV1 (group 1, p=0.04; group 2, p < 0.001), total lung capacity (TLC; group 1, p=0.02; group 2, p < 0.001), residual volume (RV; group 1, p=0.002; group 2, p < 0.001), RV/TLC ratio (group 1, p=0.03; group 2, p < 0.001), PaCO2 (group 1, p=0.002; group 2, p=0.02), 6-min walk distance (group 1, p=0.005; group 2, p < 0.001), oxygen consumption at peak exercise (group 1, p=0.02; group 2, p=0.02), total exercise time (group 1, p=0.02; group 2, p=0.02), and the perceived overall QOL scores (group 1, p=0.001; group 2, p < 0.001). However, because the magnitude of improvement was similar in both groups, and the hypercapnic group was more impaired, the spirometry, lung volumes, and 6-min walk distance remained significantly lower post-LVRS in the hypercapnic patients. There was no difference in mortality between the groups (p=0.9). Patients with moderate to severe resting hypercapnia exhibit significant improvements in spirometry, gas exchange, perceived QOL, and exercise performance after bilateral LVRS. The maximal achievable improvements in postoperative lung function are related to preoperative level of function; however, the magnitude of improvement can be expected to be similar to patients with lower resting PaCO2 levels. Patients should not be excluded from LVRS based solely on the presence of resting hypercapnia. The long-term benefit of LVRS in hypercapnic patient remains to be determined.

Chronic hypercapnia should not exclude patients from lung volume reduction surgery.

Chronic hypercapnia is still considered to increase the risk for perioperative mortality and therefore to be a contraindication for lung volume reduction surgery (LVRS). The aim of this study was to analyse the influences of hypercapnia upon postoperative outcome. The functional improvement (preop vs. 3 months postop) and clinical outcome was studied in 22 patients with chronic hypercapnia (preoperative arterial pCO2 > or = 45 mmHg) who underwent LVRS between 9/94 and 2/97 and were compared to all other patients (n = 58) without hypercapnia. Data are expressed as the mean +/- SEM. The 30-day mortality was 9.1% (2/22) in patients with chronic hypercapnia (HC) and 5.2% (3/58) in patients with normal arterial pCO2 levels (control) (P = n.s). The stay on the ICU (3.5 +/- 0.8 vs. 2.1 +/- 0.3 days) and duration of chest drainage (7.3 +/- 1.2 vs. 7.2 +/- 0.8 days) was similar between both groups (HC vs. control) (P = n.s). The preoperative lung function (% of predicted) and blood gas (mmHg) parameters were significantly worse in HC patients compared to control patients. In both groups significant functional improvements were observed: FeV1 in the control group increased by 37% within the first 3 months (29.1 +/- 1.7% of predicted vs. 39.9 +/- 3.1% of predicted, P = 0.0198). In the HC group, FeV1 increased by 73% which was even higher than in the controls (19.5 +/- 1.5% of predicted vs. 33.7 +/- 4.7% of predicted, P = 0.0385). All patients of both groups who died perioperatively had a significantly higher severity of parenchymal destruction than those who survived (P = 0.0277 and 0.0380, respectively). Patients with chronic hypercapnia alone, had no significantly higher mortality and morbidity, and therefore should not be excluded from LVRS. However, the presence of additional risk factors, such as homogeneity of disease, high degree of parenchymal destruction or pulmonary hypertension should be considered as contraindications for the procedure.

Changes in the Arterial PCO2 during a Single Night's Sleep in Patients with Obstructive Sleep Apnea.

To investigate the relationship between hypercapnia during sleep and its influence on the PaCO2 during the morning after sleep in patients with obstructive sleep apnea syndrome (OSAS), the transcutaneous PCO2 (PtcCO2) was measured throughout the night, and the arterial blood gases (ABG) were also measured while awake before and after polysomnography in 30 OSAS patients with (n=13, hypercapnic group: HC) and without (n=17, normocapnic group: NC) hypercapnia. Significant differences were observed in the body mass index (p=0.03), the difference between the highest PtcCO2 during sleep and the PtcCO2 during awake before sleep (D-PtcCO2), (HC: 11.l+/-1.7 mmHg; NC: 6.3+/-0.5 mmHg; p=0.0057) and the lowest SaO2 during sleep (p=0.0007). In the HC, the PaCO2 on the morning after sleep (50.0+/-0.14 mmHg) was significantly increased (p=0.0029) compared with the PaCO2 on the night before sleep (47.4+/-1.1 mmHg). In the NC, this phenomenon was not observed. Severe hypercapnia (high D-PtcCO2) during a single night's sleep has a significant effect on the waking PaCO2 immediately following sleep in the HC.

A physical–chemical analysis of the acid–base response to chronic obstructive pulmonary disease

The metabolic contributions to chronic acid-base changes were examined in the plasma of arterial blood in patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia, by a quantitative physical-chemical analysis. Patients were stratified into three groups: group 1 (Paco2 less than 40 mmHg; 1 mmHg = 133.3 Pa), group 2 (Paco2 between 40 and 50 mmHg), and group 3 (Paco2 higher than 50 mmHg). With the development of hypercapnia (Paco2 from 38.2 +/- 1.6 to 53.8 +/- 0.6 mmHg) and hypoxemia (Pao2 from 73.6 +/- 2.5 to 62.1 +/- 2.1 mmHg), blood pH decreased slightly (from 7.405 +/- 0.007 to 7.372 +/- 0.009). The strong ion difference ([SID]) increased in the hypercapnic group (from 39.7 +/- 1.7 to 46.2 +/- 2.9 mequiv.L-1) parallel to the increase in [HCO3-] (from 23.8 +/- 0.5 to 30.8 +/- 0.8 mequiv.L-1). The change in [SID] was quantitatively similar to the [HCO3-] change, thus reflecting a metabolic compensation of chronic respiratory acidosis. [SID] increase was mainly accounted for by changes in the [Na+]/[Cl-] ratio due to a significant decrease in plasma [Cl-]. Other ions measured as well as the weak acid buffers ([ATOT]) remained constant. From the present results, we suggest the usefulness of the physical chemical approach in the characterization of acid-base disturbances due to chronic hypercapnia when water retention or protein depletion are expected further to hypochloremia, as can be the case in severe COPD patients.

Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia.

To ascertain whether and to what extent the reduced ventilatory response to a hypercapnic stimulus in chronic obstructive pulmonary disease (COPD) patients depends on a blunted chemoresponsiveness of central origin or to mechanical impairment, we studied two groups of COPD patients without (group A) and with (group B) chronic hypercapnia, but with similar degrees of airway obstruction and hyperinflation. The study was performed on 17 patients (9 normocapnic and 8 hypercapnic). Six age-matched normal subjects (group C) were also studied as a control. During a CO2 rebreathing test, ventilation (VE), mouth occlusion pressure (P0.1), and the electromyographic activity of diaphragm (Edi) were recorded and then plotted against end-tidal carbon dioxide tension (PCO2). Inspiratory muscle strength was significantly lower in the hypercapnic group (group B) compared to normocapnic group (A), and in these groups compared to the control group (C). Both patient groups exhibited significantly lower delta VE/delta PCO2 than the control group. In hypercapnics, delta P0.1/delta PCO2 was significantly lower than in normocapnics and control group, whilst mouth occlusion pressure as % of maximal inspiratory pressure delta P0.1 (% MIP)/delta PCO2 did not differ significantly among the three groups. delta Edi/delta PCO2 increased from C to A. At a PCO2 of 8.65 kPa, VE was similar in the normocapnic and control group, but lower in hypercapnics; Edi was similar in hypercapnic and control group; but greater in normocapnics. P0.1(% MIP) did not differ significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

IVOX with Gradual Permissive Hypercapnia: A New Management Technique for Respiratory Failure

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 ± 4 mm Hg vs 51 ± 3 mm Hg and 3.9 ± 0.3 liters vs 8.4 ± 0.5 liters (P < 0.05) respectively. CO2 removal by IVOX can be substantially augmented under conditions of permissive hypercapnia, reducing the ventilatory requirements in an ovine model of acute smoke inhalation injury.

External High-Frequency Ventilation in Severe Chronic Obstructive Pulmonary Disease

We studied the effect of external high-frequency oscillation using an oscillator (Hayek oscillator [HO]) on 20 patients with severe chronic obstructive pulmonary disease (COPD). Of the 20 patients, 10 were eucapnic and 10 were hypercapnic. The HO generated frequencies from 60 to 140 cycles/min at an amplitude of 36 cm H2O (-26 to +10) and at an inspiratory/expiratory (I/E) ratio of 1:1. The results show that the HO is a powerful ventilator, reducing end-tidal PCO2 (PETCO2) by 6.7 to 9.1 mm Hg in eucapnic patients and by 6.1 to 7.9 mm Hg in hypercapnic patients. The oxygen saturation increased by 2 to 2.87 percent in the eucapnic patients and by 2.6 to 3.7 percent in the hypercapnic group in the various frequencies. The rate of elimination of CO2 and the levels of PETCO2 achieved within a short time were superior to those reported with other external ventilators. We conclude that the HO can be effectively used in severe COPD and respiratory failure for (1) assisting ventilation, thus replacing intubation and conventional mechanical ventilation, and (2) relieving muscle fatigue in short sessions.

Changes in Brain Capillary Diameter during Hypocapnia and Hypercapnia

Since changes in the surface area of capillaries may be relevant to capillary exchange, the distensibility of brain capillaries was investigated. Brain capillary diameters were measured after perfusion fixation of brain tissue at a constant perfusion pressure during hypo- or hypercapnia. Sections were embedded, stained, and analyzed by light microscopy. The results showed significant differences in mean capillary diameter between the hypocapnic and the hypercapnic group. In the eight brain structures analyzed, capillary diameters were always larger in the hypercapnic group. Mean capillary diameter was 4.93 +/- 0.29 microns in the hypocapnic group and 5.91 +/- 0.10 microns in the hypercapnic group (means +/- SD). We conclude that brain capillaries exhibit a moderate degree of distensibility. Variations in the precapillary pressure of microvessels may therefore influence both capillary flow and capillary surface area.

Influence of hypoxic and hypercapnic acidosis on brain water content after forebrain ischemia in the rat

To determine whether hypoxia or hypercapnia superimposed on ischemia affects brain water content after ischemia. Prospective, randomized, controlled trial. Thirty-one male Wistar rats. The rats were assigned randomly into one of six groups: a) control; b) ischemia; c) ischemia combined with hypoxia; d) ischemia combined with hypercapnia; e) hypoxia; f) hypercapnia. Forebrain ischemia was induced for 5 mins by clamping both carotid arteries and inducing exsanguination. Either hypoxia or hypercapnia was induced until the arterial pH decreased to 7.0. The rats were decapitated after the protocol. After the decapitation, the specific gravities of the neocortex, caudatoputamen, hippocampus, cerebellum, and midbrain were measured using a variable-density bromobenzene-kerosene column technique as an index of brain swelling. The specific gravities of the hippocampus and the neocortex were significantly lower in the ischemic group than in the control group. Specific gravities of the caudatoputamen and neocortex in the ischemia plus hypercapnia group, and specific gravities of the caudatoputamen, neocortex, and hippocampus in the ischemia plus hypercapnia group, were significantly lower than in the ischemia group. Cerebral water content increases more when ischemia is accompanied by hypoxia or hypercapnia than after ischemia alone. Hypoxic and/or hypercapnic acidosis during the periresuscitation period may be one of the causes of brain swelling after the resuscitation of patients after an anoxic-ischemic insult.

CENTRAL SLEEP APNEA

The critical issue in considering the diagnosis and management of CSA is to determine the physiologic process underlying the disorder. CSA includes a pathophysiologically and clinically heterogeneous group of disorders that can be divided into two main groups on the basis of the awake PaCO2: a hypercapnic group, in whom the disorder is related to central alveolar hypoventilation or neuromuscular disease, and a nonhypercapnic group, in whom there is no identifiable underlying disorder. The common feature of these two groups is recurrent episodes of central apnea during sleep related to withdrawal of the wakefulness drive to breathing. In the hypercapnic group the clinical history is dominated by recurrent episodes of respiratory failure and its complications, with the sleep disturbance being a secondary feature. CSA in these patients is simply an exaggeration, by sleep, of their hypoventilation disorder. Treatment in most cases involves mechanical assisted ventilation during sleep, which can be very effective in reversing CSA and respiratory failure. In contrast, idiopathic CSA is characterized by a tendency to hyperventilation. This tendency is reinforced during sleep by recurrent arousals, which tend to propagate the CSA. Unlike hypercapnic CSA, idiopathic CSA is a relatively benign condition in which cardiorespiratory failure is not a feature. Treatment of this disorder is problematic, but the use of nocturnal nasal CPAP appears to be quite effective.

Pulmonary blood volume and haemodynamic changes with legs raised in chronic lung disease patients

The aim was determine the early effect of a posture change from supine (S) to legs raised 30 degrees above the table plane (LR) on haemodynamics in patients with chronic lung disease. Right heart catheterization was performed as part of a routine evaluation. Pulmonary arterial, pulmonary wedge, right atrial, and systemic arterial pressure were monitored at rest supine and during 8 min (steady values) after LR. Pulmonary blood volume was measured by double dye dilution, at rest S and after 1 and 8 minutes LR, in 14 patients; cardiac output was measured by thermodilution in the remaining 15 subjects, during S and 1, 4, and 8 minutes LR. 29 patients with chronic pulmonary disease of various types, mainly chronic bronchitis and emphysema, were studied when in a stable clinical condition, with no signs of heart failure. Raising the legs produced a sharp increase in all the pressures measured, with a subsequent decline towards a steady value slightly higher than during S. Pulmonary blood volume increased in all patients initially, but stayed elevated only in the normocapnic patients; in the patients with hypercapnia it decreased from 1 to 8 min LR. The pulmonary blood volume change showed a significant correlation with PaCO2 (p less than 0.01), and with the VD/VT ratio (p less than 0.01). The relation between the pulmonary blood volume and the distending pressure changes from S to 1 and 8 min LR was linear in the normocapnic group, but not in the hypercapnic group, where it showed a hysteresis. In patients with chronic lung disease who are hypercapnic, the volume/pressure relation following leg raising cannot be expressed by a single distensibility coefficient.

Eucapnia and Hypercapnia in Patients with Chronic Airflow Limitation: The Role of the Upper Airway

In this study, we examined two groups of patients with chronic airflow limitation (CAL) separated according to their awake, stable arterial CO2 level. The aim was to identify factors that may contribute to the development of chronic hypercapnic respiratory failure. Patients with obstructive sleep apnea were excluded from the study. Detailed lifetime histories of smoking, alcohol, and snoring were obtained from all patients together with measurements of lung function and of upper airway size. Thirty-three patients with FEV1 less than 1.5 L were studied, of whom 19 were eucapnic and 14 were hypercapnic. Both groups had a similar degree of chronic airflow limitation and similar lung volumes and DLCO. The hypercapnic group had more hypopneas and desaturated more severely during sleep. The greatest differences between the groups were in their alcohol consumptions, snoring histories, and upper airway dimensions. The eucapnic patients were characterized by lower lifetime alcohol intake, minimal snoring, and large upper airway size. In contrast, the hypercapnic patients were characterized by excessive lifetime alcohol consumption, habitual snoring over many years, and a small upper airway size. Our findings suggest that chronic, heavy alcohol use and upper airway dysfunction are important factors in the development of hypercapnic respiratory failure.