Fall In PaCO2 Research Articles

S65 Interim data from a randomised controlled trial of average volume-assured pressure support (AVAPS) versus spontaneous-timed (ST) pressure support in Obesity Hypoventilation Syndrome (OHS)

IntroductionThe obesity epidemic is leading to an increase in respiratory morbidity including sleep disordered breathing (SDB). The optimal ventilatory strategy in OHS is yet to be characterised. Changes in the...

Arterial [H+] and the ventilatory response to hypoxia in humans: influence of acetazolamide-induced metabolic acidosis

In this study, we investigated possible separate effects of H+ ions and CO2 on hypoxic sensitivity in humans. We also examined whether hypoxic sensitivity, conventionally defined as the ratio of (hypoxic - normoxic) ventilation over (hypoxic - normoxic) Hb oxygen saturation can also be estimated by taking the ratio (hypoxic - normoxic) ventilation over (logPa(O2) hypoxia - logPa(O2) normoxia), enabling one to measure the hypoxic response independently from potential confounding influences of changes in position of the Hb oxygen saturation curve. We used acetazolamide to induce a metabolic acidosis. To determine the acute hypoxic response (AHR), we performed step decreases in end-tidal Po2 to approximately 50 Torr lasting 5 min each at three different constant end-tidal Pco2 levels. Nine subjects ingested 250 mg of acetazolamide or placebo every 8 h for 3 days in a randomized double-blind crossover design. The metabolic acidosis was accompanied by a rise in ventilation, a substantial fall in Pa(CO2), and a parallel leftward shift of the ventilatory CO2 response curve. In placebo, CO2 induced equal relative increases in hypoxic sensitivity (O2-CO2 interaction) regardless of the way it was defined. Acetazolamide shifted the response line representing the relationship between hypoxic sensitivity and arterial [H+] ([H+](a)) to higher values of [H+](a) without altering its slope, indicating that it did not affect the O2-CO2 interaction. So, in contrast to an earlier belief, CO2 and H+ have separate effects on hypoxic sensitivity. This was also supported by the finding that infusion of bicarbonate caused a leftward shift of the hypoxic sensitivity-[H+](a) response lines in placebo and acetazolamide. A specific inhibitory effect of acetazolamide on hypoxic sensitivity was not demonstrated.

Complex Sleep Apnea: It Isn't Really a Disease

Complex Sleep Apnea: It Isn't Really a Disease

Effects of Noninvasive Ventilation on Pulmonary Gas Exchange and Hemodynamics during Acute Hypercapnic Exacerbations of Chronic Obstructive Pulmonary Disease

Noninvasive positive pressure ventilation (NIPPV) can replace tracheal intubation in acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hypercapnic respiratory failure. However, the underlying mechanisms by which NIPPV improves pulmonary gas exchange are not known. We studied 10 male COPD patients (68 +/- 8 [SD] yr) with acute severe hypercapnic respiratory failure within 36 h after hospital admission. Measurements of pulmonary gas exchange, hemodynamics, and respiratory mechanics were done: (I) breathing spontaneously (baseline); (2) after 15 and 30 min of NIPPV with pressure support (inspiratory pressure = 12 +/- 2 cm H20, PEEP = 3 +/- 2 cm H20); and (3) 15 min after NIPPV withdrawal. Patients were ventilated using a full face mask, keeping FIO2 constant (0.23 +/- 0.02) in all conditions. Compared with baseline, during NIPPV (15 min) we observed a moderate increase in Pa02 (from 50 +/- 6 to 57 +/- 9 mm Hg; p < 0.05), and a fall in PaCO2 (from 66 +/- 10 to 59 +/- 10 mm Hg; p < 0.0001), but AaPO2 increased (from 39 +/- 13 to 48 +/- 13 mm Hg; p < 0.001). Breathing frequency decreased (from 26 +/- 5 to 19 +/- 3 breaths/min; p < 0.0001), tidal volume increased (from 311 +/- 42 to 520 +/- 133 ml; p < 0.0001), and minute ventilation increased (from 8.0 to 1.7 to 9.6 +/- 2.0 L/min; p < 0.05). Cardiac output fell during NIPPV in all patients (from 6.7 +/- 1.6 to 5.8 +/- 1.3 L/min; p < 0.0025) with no impact on mixed venous PO2. No substantial changes in VA/Q mismatching (multiple inert gas elimination technique) were observed. While oxygen uptake showed a trend to decrease, the respiratory exchange ratio (R) increased (from 0.78 +/- 0.17 to 0.90 +/- 0.22; p < 0.001). The effects of NIPPV were unchanged at 30 min compared with 15 min and were reversed after 15 min of NIPPV withdrawal. We conclude that improvement in respiratory blood gases during NIPPV is essentially due to higher alveolar ventilation (p < 0.001) and not to improvement in VA/Q relationships. The increase in AaPO2 was explained by the rise in R due to an increased clearance of body stores of C02 during NIPPV. Our results indicate that attainment of an efficient breathing pattern rather than high inspiratory pressures should be the primary goal to improve arterial blood gases during NlPPV in this type of patient.

Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat: Br J Pharmacol 1996; 118/1: 198–204

1. This study investigates the effects of the non-selective ETA/ETB receptor antagonist, SB 209670, on systemic haemodynamics, renal function, liver function, acid-base balance and survival in a rat model of endotoxic shock. 2. Injection of E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.) resulted in increases in the serum levels of tumour necrosis factor-alpha (TNF-alpha, maximum 60 min after LPS), endothelin-1, (ET-1; maximum 120 min after LPS), and interferon-gamma (IFN-gamma, maximum 180 min after LPS). 3. Injection of LPS also resulted in a fall in blood pressure from 113 +/- 3 mmHg (time = 0) to 84 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the vasoconstrictor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with a continuous infusion of SB 209670 (3 mg kg-1, i.v. bolus + 100 micrograms kg-1, i.v. infusion commencing 15 min prior to LPS) significantly augmented the hypotension as well as the vascular hyporeactivity to NA caused by endotoxaemia. 4. Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus given 15 min prior to LPS) or infusion of SB 209670 (bolus dose and infusion as above) resulted in a reduction in 6 h-survival from 71% (control) to 30% and 13%, respectively. 5. Endotoxaemia for 4 h resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), but not in the serum levels of bilirubin, GPT and GOT (indicators of liver dysfunction and/or hepatocellular injury). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus 15 min prior to LPS) significantly augmented the serum levels of creatinine, bilirubin, GPT and GOT caused by endotoxin. In addition, endotoxaemia caused, within 15 min, an acute metabolic acidosis (falls in pH, HCO3- and base excess) which was compensated by hyperventilation (fall in PaCO2). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus) significantly augmented the metabolic acidosis caused by LPS. 6. Thus, the non-selective ETA/ETB receptor antagonist, SB 209670, augments the degree of (i) hypotension, (ii) vascular hyporeactivity to noradrenaline, (iii) renal dysfunction and (iv) metabolic acidosis caused by endotoxin in the anaesthetized rat. In contrast to rats treated with LPS alone, LPS-rats treated with SB 209670 exhibited liver dysfunction and hepatocellular injury. We propose that the release of endogenous ET-1 serves to maintain blood pressure and subsequently organ perfusion in septic shock.

The biphasic ventilatory response to hypoxia in preterm infants is not due to a decrease in metabolism

The mechanism underlying the biphasic ventilatory response to hypoxia in neonates is poorly understood. Because alveolar PCO2 (PACO2) decreases and remains low during hypoxia, it has been argued that a decrease in metabolism may occur. We hypothesized that if the late decrease in ventilation during hypoxia is due to a decrease in CO2 production, an increase in PACO2 should abolish it. We studied 27 preterm infants [birth weight, 1,700 ± 41 g (mean ± SEM); study weight, 1,760 ± 36 g; gestational age 32 ± 0.2 weeks; postnatal age, 17 ± 1 days]. A flow-through system and Beckman analyzers were used to measure ventilation and alveolar gases. Metabolism was expressed as changes in oxygen consumption. Infants were studied randomly during hypoxia alone (15% O2 + N2, n = 55) and during hypoxia plus CO2, (0.5% CO2, n = 30; 2% CO2, n = 10). Each experiment consisted of 2 minutes of control measurements (21% O2), 5 minutes of measurements during hypoxia alone or hypoxia plus CO2, followed by 2 minutes of recovery (21% O2). We found a biphasic response to hypoxia with or without CO2 supplementation, the percent change in ventilation from initial peak hyperventilation to late hypoventilation at 5 minutes being -16 ± 2 on 15% O2; -9 ± 3 on 15% O2; + 0.5% CO2 and -15 ± 9 on 15% O2; + 2% CO2; (P < 0.05).The decrease in ventilation was primarily due to a significant decrease in frequency; tidal volume increased. Oxygen consumption decreased similarly with the various inspired gas mixtures during hypoxia. These findings indicate that the decrease in ventilation during hypoxia is unlikely to be solely due to a decrease in metabolism since the late decrease in ventilation following initial hyperventilation still occurred despite the elimination of a fall in PACO2. We speculate that the mechanism underlying the late decrease in ventilation is likely of central origin, probably mediated through the release of inhibitory neurotransmitters. Pediatr Pulmonol. 1996; 22:287–294. © 1996 Wiley-Liss, Inc.

Effect of selective blockade of endothelin ETB receptors on the liver dysfunction and injury caused by endotoxaemia in the rat.

1. We investigated the effects of the selective endothelin (ET)A receptor antagonist BQ-485 and the selective ETB receptor antagonist BQ-788 on circulatory failure, multiple organ dysfunction syndrome (MODS) and the alterations in acid base balance caused by endotoxaemia in the anaesthetized rat. 2. Male Wistar rats were anaesthetized (thiopentone sodium; 120 mg kg-1, i.p.) and received a continuous infusion of vehicle (saline, 0.6 ml kg-1h-1, i.v.), BQ-485 (10 nmol kg-1 min-1, i.v.) or BQ-788 (10 nmol kg-1 min-1, i.v.). Fifteen min later, animals received a bolus injection of either saline (0.9% NaCl, 1 ml kg-1, i.v.) or E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.). 3. Injection of LPS resulted in a fall in blood pressure from 115 +/- 4 mmHg (time 0) to 82 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the pressor responses to noradrenaline (NA, 1 microgram kg-1, i.v.). Infusion of BQ-788 attenuated the delayed hypotension (at 360 min: 100 +/- 4 mmHg, n = 7; P < 0.05) and significantly enhanced the pressor responses elicited by NA (at 60 to 240 min). In contrast, treatment of LPS-rats with BQ-485 augmented the hypotension (at 360 min), but did not affect the vascular hyporeactivity elicited by endotoxaemia. 4. Endotoxaemia for 360 min resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), glutamate-oxalate-transferase (GOT) and glutamate-pyruvate-transferase (GPT) (indicators of hepatocellular injury), and bilirubin and gamma-glutamyl transferase (gamma GT) (indicators of liver failure) as well as nitrite (indicator of the induction of nitric oxide synthase; iNOS). Treatment of LPS-rats with BQ-788, but not with BQ-485, attenuated the degree of liver injury and failure, while neither BQ-788 nor BQ-485 affected the acute renal failure or the induction of iNOS caused by endotoxin. 5. Endotoxaemia also caused (within 15 min) an acute metabolic acidosis (falls in pH, HCO3-and base excess) which was compensated by hyperventilation (fall in PaCO2). Treatment of LPS-rats with BQ-788 or BQ-485 did not affect the metabolic acidosis caused by LPS. 6. Thus, the selective ETB receptor antagonist BQ-788 attenuated (i) the delayed hypotension, (ii) the vascular hyporeactivity to NA as well as (iii) the degree of hepatocellular injury and dysfunction caused by endotoxin in the anaesthetized rat. In contrast, the selective ETA receptor antagonist did neither attenuate the circulatory failure nor the liver or renal dysfunction associated with endotoxaemia. We propose that the prevention of the hepatocellular dysfunction and injury caused BQ-788 in endotoxaemia is due to an improvement in oxygen delivery to the liver secondary to (i) inhibition of pre-sinusoidal constriction, (ii) inhibition of sinusoidal constriction, and (iii) improvement in perfusion pressure.

Limited role for nitric oxide in mediating cerebrovascular control of newborn piglets.

To investigate the effects of the nitric oxide (NO) synthase inhibitor L-nitro-arginine methyl ester (L-NAME) on cerebral blood flow, and its response to alterations in arterial carbon dioxide tension (CBF-CO2 reactivity). Cerebral blood flow was measured six times at varying arterial carbon dioxide tension (PaCO2) using the intravenous 133Xenon clearance technique in eight mechanically ventilated piglets of less than 24 hours postnatal age. After the third measurement L-NAME was administered as a bolus (20 mg/kg) and subsequently infused (10 mg/kg/hour). PaCO2 ranged between 2.7-8.9 kPa. Cerebral blood flow decreased by 14.0% (95% confidence interval 1.9-27.4) after L-NAME. CBF-CO2 reactivity was 18.4% per kPa (95% CI 14.1-22.2) before L-NAME and 15.2%/kPa (95% CI 11.1-19.3) afterwards; the difference between the CBF-CO2 reactivities was 3.2%/kPa (95% CI -0.4-6.8): these were not significantly different. Inhibition of nitric oxide synthesis reduces cerebral blood flow no more than a 0.5-1.0 kPa fall in PaCO2. Nitric oxide is not an important mediator of CBF-CO2 reactivity.

Benefits of the low pressure multichannel endotracheal ventilation.

Mechanical ventilation using a modified endotracheal tube, allowing bypass and washout of the endotracheal dead space (McETV), was compared with conventional controlled mechanical ventilation (CMV) in healthy and in surfactant-depleted rabbits. In healthy animals, shifting from CMV to McETV led to an increase in PaO2 (89 +/- 16 versus 104 +/- 13 mm Hg; p < 0.05) and a decrease in PaCO2 (41.5 +/- 3 versus 30 +/- 3 mm Hg; p < 0.05). As a result of reducing the peak inspiratory pressure (PIP) from 21 +/- 2 to 12 +/- 2 cm H2O (p < 0.05), it was possible in McETV mode to maintain comparable ventilation to that achieved by CMV. In surfactant-depleted animals, compared with CMV, McETV produced a rise in PaO2 without change in thoracic volume (from 100 +/- 40 to 150 +/- 60 mm Hg, p < 0.05) and a fall in PaCO2 (from 46 +/- 5 to 37 +/- 4 mm Hg, p < 0.05). After 4 h of ventilation, the surfactant-depleted animals from the CMV group developed thoracic overdistension quicker (at hour 1, p < 0.05) and, consequently, more animals died from pneumothorax compared with the McETV group (five versus two). We concluded that McETV ensured adequate gas exchanges with lower insufflation pressures and could diminish positive pressure ventilation-induced injury.

Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat.

1. This study investigates the effects of the non-selective ETA/ETB receptor antagonist, SB 209670, on systemic haemodynamics, renal function, liver function, acid-base balance and survival in a rat model of endotoxic shock. 2. Injection of E. coli lipopolysaccharide (LPS, 10 mg kg-1, i.v.) resulted in increases in the serum levels of tumour necrosis factor-alpha (TNF-alpha, maximum 60 min after LPS), endothelin-1, (ET-1; maximum 120 min after LPS), and interferon-gamma (IFN-gamma, maximum 180 min after LPS). 3. Injection of LPS also resulted in a fall in blood pressure from 113 +/- 3 mmHg (time = 0) to 84 +/- 4 mmHg at 360 min (n = 15) as well as a hyporeactivity to the vasoconstrictor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with a continuous infusion of SB 209670 (3 mg kg-1, i.v. bolus + 100 micrograms kg-1, i.v. infusion commencing 15 min prior to LPS) significantly augmented the hypotension as well as the vascular hyporeactivity to NA caused by endotoxaemia. 4. Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus given 15 min prior to LPS) or infusion of SB 209670 (bolus dose and infusion as above) resulted in a reduction in 6 h-survival from 71% (control) to 30% and 13%, respectively. 5. Endotoxaemia for 4 h resulted in rises in the serum levels of urea and creatinine (indicators of renal failure), but not in the serum levels of bilirubin, GPT and GOT (indicators of liver dysfunction and/or hepatocellular injury). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus 15 min prior to LPS) significantly augmented the serum levels of creatinine, bilirubin, GPT and GOT caused by endotoxin. In addition, endotoxaemia caused, within 15 min, an acute metabolic acidosis (falls in pH, HCO3- and base excess) which was compensated by hyperventilation (fall in PaCO2). Pretreatment of LPS-rats with SB 209670 (3 mg kg-1, i.v. bolus) significantly augmented the metabolic acidosis caused by LPS. 6. Thus, the non-selective ETA/ETB receptor antagonist, SB 209670, augments the degree of (i) hypotension, (ii) vascular hyporeactivity to noradrenaline, (iii) renal dysfunction and (iv) metabolic acidosis caused by endotoxin in the anaesthetized rat. In contrast to rats treated with LPS alone, LPS-rats treated with SB 209670 exhibited liver dysfunction and hepatocellular injury. We propose that the release of endogenous ET-1 serves to maintain blood pressure and subsequently organ perfusion in septic shock.

Haemodynamic effects of atrial natriuretic peptide in hypoxic chronic obstructive pulmonary disease.

Pulmonary artery pressure is elevated in patients with advanced chronic obstructive pulmonary disease (COPD). Release of atrial natriuretic peptide (ANP) is increased in pulmonary hypertension and this hormone may both selectively vasodilate pulmonary vessels and inhibit pulmonary vascular remodelling. The hypothesis that ANP has a physiological role in protection of the pulmonary circulation from pressure overload, and that it may be beneficial in patients with COPD, has been examined. Ten patients with hypoxic COPD were infused for 30 minute periods with saline followed by ANP at 0.4, 2, and 10 pmol/kg/min respectively via a pulmonary artery catheter whilst monitoring haemodynamics and oxygenation. Levels of immunoreactive ANP (irANP) increased from a mean (SD) of 23 (15) pmol/l to a maximum of 94 (41) pmol/l. Neither systemic blood pressure, cardiac output nor total systemic vascular resistance showed any correlation with irANP levels. There were negative correlations between levels of ANP and mean pulmonary artery pressure which fell from 28.7 to 25.9 mm Hg, pulmonary artery wedge pressure which fell from 6.5 to 4.6 mmHg, and total pulmonary vascular resistance which fell from 489 to 428 dynes s cm-5. There was a small fall in PaCO2 from 6.2 to 5.9 kPa, whilst venous admixture and oxygen delivery both increased non-significantly. At these pathophysiological concentrations there was evidence that ANP selectively reduced right ventricular afterload. These data support the hypotheses that increased plasma levels of ANP may be beneficial in hypoxic COPD, and that endogenous ANP may ameliorate pulmonary hypertension in humans.

Influence of intravenously administered lidocaine on cerebral blood flow in a baboon model standardized under controlled general anaesthesia using single-photon emission tomography and technetium-99m hexamethylpropylene amine oxime

The baboon under general anaesthesia as a model to assess drug-induced cerebral blood flow changes (delta CBF) using single-photon emission tomography (SPET) offers great in vivo possibilities but has to comply with demands on control of anaesthesia-related influencing factors, such as PaCO2 changes. The model sought in this study and described here allows control of PaCO2, in the baboon under thiopentone anaesthesia by ventilation, and was evaluated for the functional dependence of delta CBF vs delta PaCO2, using SPET technetium-99m hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with controlled ventilation. During the experiment the model was validated for normal reactivity to PaCO2 changes, and subsequently applied to investigate the mechanisms (still uncertain) of CBF increase known to follow administration of the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine intravenously. CBF was measured between two consecutive SPET acquisitions (split-dose method) respectively relating to HM-PAO distributions in the brain before and after the injection of lidocaine. Meanwhile the animals were maintained at constant respiratory rate and volume. The results indicate that the correlation between delta CBF and the ensuing fall in PaCO2 deviated from the baseline pattern from the model and confirmed a cerebrovascular contribution to the lidocaine-induced CBF increase. This agreed well with mean and systolic blood pressure changes and heart rate.

Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease

Acute exacerbations of chronic obstructive airways disease (COAD) are a common cause of admission to hospital, and have a high mortality. Nasal intermittent positive pressure ventilation (NIPPV) has been used successfully in patients with respiratory failure due to neuromuscular and skeletal disorders, but the outcome of treatment in patients with COAD is less well known. We carried out a prospective randomised controlled trial of conventional treatment versus conventional treatment plus NIPPV, in 60 patients with acute ventilatory failure due to exacerbations of COAD. For the NIPPV group there was a rise in pH, compared with a fall in the controls (mean difference of change between the groups 0·046 [95% Cl 0·06-0·02, p<0·001]), and a larger fall in PaCO2 (mean difference in change between the groups 1·2 kPa [95% Cl 0·45 to 2·03, p<0·01]). Median visual analogue scores over the first 3 days of admission showed less breathlessness in the NIPPV group (2·3 cm [range 0·1-5·5]) than in the control group (4·5 cm [range 0·9-8·8]) (p<0·025). Survival rates at 30 days were compared for intention-to-treat and efficacy populations. In the efficacy mortality comparison, mortality in the NIPPV group was reduced: 1/26 vs 9/30 (relative risk=0·13, CI=0·02-0·95, p=0·014). This effect was less in the intention-to-treat analysis: 3/30 vs 9/30 (relative risk=0·33, CI=0·10-1·11, p=0·106). In patients with acute ventilatory failure due to COAD who received NIPPV there was a significant rise in pH, a reduction in PaCO2 and breathlessness, and reduced mortality.

Early results of intravascular oxygenation

We have used the intravascular oxygenator (IVOX) in eight patients (14-76 years) with acute respiratory failure. At the time of referral for IVOX all patients were on inotropic support, five had pneumothoraces and two were on haemofiltration. Ventilatory data before IVOX were: ventilated for 2-14 days (median 6), PEEP 5-12 cm H2O (12), PIP 34-95 cm H2O (49), FiO2 0.7-1 (1), PaO2 5.4-26 KPa (8.5) and PaCO2 3.7-23 KPa (8). The intravascular oxygenator was used for 6 h-12 days (median 4), the oxygen transfer achieved was 68-140 ml/min (85) and the carbon dioxide removed was 40-106 ml/min (59). It was possible to decrease the ventilator settings with a significant increase in the PaO2 by 48 h (P < 0.05) but the fall in PaCO2 did not reach significance. As the IVOX was turned from "off" to "on" the mean PaO2 increase was 0.35 KPa +/- 0.14 SEM (P = 0.04) and the mean PaCO2 decrease 0.7 KPa +/- 0.2 SEM (P = 0.02) without any significant change in cardiac output. Two patients survived and six died from multisystem failure with three patients being hypoxic at the time of death. Postmortem examinations on five patients did not reveal any IVOX-related complications. We conclude that IVOX is safe but it is not as efficient in gas exchange as extracorporeal membrane oxygenation at present. Further improvement in the gas exchange efficiency of this prototype could render IVOX a very useful device.

Voluntary Hyperventilation in Obesity Hypoventilation*

Arterial blood gas analysis was performed before and after 60 to 90 s of voluntary hyperventilation in 27 consecutive patients with occlusive sleep apnea syndrome (OSA) and daytime hypercapnia. The percentage of fall in PaCO2 from baseline was examined in relationship to age, body mass index, sleep-disordered breathing indices, and pulmonary function variables. In 14 subjects without airflow obstruction, only one individual could not voluntarily hyperventilate into the normal range, whereas 6 of 13 subjects with airflow obstruction could not hyperventilate to eucapnia. The average percentage of fall in PaCO2 was 16 mm Hg (SEM = 1.3 mm Hg). The percentage of fall in PaCO2 correlated significantly with FEV1/FVC ratio (r = 0.47, p = 0.01) and with FEV1 (r = 0.5, p = 0.008). Although the baseline PaCO2 did not correlate with FEV1, the posthyperventilation PaCO2 did (r = 0.54, p = 0.003). Voluntary hyperventilation studies herein suggest a predominant role for impairment of ventilatory control in the maintenance of hypercapnia in OSA since a fall of PaCO2 into the normal range can usually be obtained. The correlation between the percentage of fall in PaCO2 and spirometric measures of respiratory mechanics, as well as the inability of some subjects to normalize the PaCO2 voluntarily suggests an added role for respiratory mechanical impairment in obesity hypoventilation.

The effects of naloxone on the cardiovascular and respiratory effects of centrally administered corticotrophin releasing factor in conscious rabbits

1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) administration of corticotrophin releasing factor (CRF) (0.5 nmol kg-1) were examined in conscious rabbits. The effect of opioid receptor antagonism was examined to determine whether the responses to CRF were mediated by endogenous opioid peptides. 2. After i.c.v. CRF there was a rise in mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline and adrenaline, and increased behavioural activity. Respiration rate increased, PaCO2 fell, but PaO2 was unchanged. 3. The pressor and behavioural effects of i.c.v. CRF were unaltered by high doses of intravenous naloxone (9 mumols kg-1 bolus followed by 9 mumols kg-1 min-1 infusion); these effects of CRF were also not prevented by double this dose of naloxone. Naloxone attenuated the CRF-induced tachycardia, blocked the increase in respiration rate and increased the fall in PaCO2. 4. After i.c. CRF (0.5 nmol kg-1) there were similar changes in MAP, HR, plasma catecholamines, respiration and behaviour. 5. These results indicate that in conscious rabbits the pressor effects of i.c.v. CRF are not mediated by endogenous opioid peptides. The finding that the effects of CRF were similar after i.c.v. and i.c. administration suggests that these responses may result from actions on brainstem rather than periventricular sites.

Transition from Exercise to Rest: Ventilatory and Arterial Blood Gas Responses

The mechanisms leading to rapid changes in arterial blood gas values soon after exercise ends have not been well established. To further study these phenomena, we exercised seven normal male volunteers to exhaustion on a cycle ergometer with a 25-W/min ramped protocol measuring arterial blood gas values, and breath-by-breath gas exchange from rest to exercise and through 15 minutes of recovery. Arterial PO2 (PaO2) increased from 108 mm Hg at peak exercise to 125 mm Hg at 2 minutes of recovery. There was a smaller rise in calculated alveolar PO2 (PAO2) from 121 to 128 mm Hg over the same period. Arterial PCO2 (PaCO2) fell from 35.0 mm Hg to 31.9 mm Hg. The gas exchange ratio R rose from 1.21 to 1.52, after having peaked at 1.68 at 1 minute. The alveolar-arterial O2 gradient (P[A-a]O2) fell from 12.3 mm Hg at peak exercise to 3.2 mm Hg at 2 minutes. Following exercise, the rise in R is related to a more rapid fall in O2 uptake than in CO2 output, and the fall in P(A-a)O2 is probably related to improved V/Q relationships and to a rise in mixed venous PO2. We conclude that the rise in PaO2 in the recovery period after progressive nonsteady state exercise is due to several factors, including a fall in P(A-a)O2 and a rise in PAO2 due primarily to an elevation of R and also to a fall in PaCO2.

Effect of negative pressure ventilation on arterial blood gas pressures and inspiratory muscle strength during an exacerbation of chronic obstructive lung disease.

The effects of intermittent negative pressure ventilation have been studied in 20 patients with chronic obstructive pulmonary disease during an exacerbation of their disease. Measurements of arterial blood gas tensions and maximal inspiratory pressure (MIP) were performed before and after six hours of negative pressure ventilation or standard treatment (control day) given in random order on two consecutive days. After negative pressure ventilation the mean (SD) value of MIP increased from 68.1 (21.5) to 74.8 (20) cm H2O;* arterial oxygen tension (PaCO2) fell from 60.6 (12.2) to 50.9 (8.9) mm Hg* but PaO2 changed little (from 48.4 (7.4) to 47.6 (8.2) mm Hg). There were no significant changes on the control day in arterial blood gas tensions (PaO2 47.8 (8.1) and 48.9 (9.4) and Paco2 59.8 (10.9) and 57.5 (8.06) mm Hg) or in MIP (69.4 (22.4) and 70.9 (22.9) cm H2O). Six patients tolerated negative pressure ventilation poorly and these patients showed less improvement after negative pressure ventilation. Our results suggest that intermittent negative pressure ventilation can increase alveolar ventilation in patients with an exacerbation of chronic obstructive lung disease, particularly in those who tolerate the procedure well. Most subjects showed a fall in PaCO2 and an increase in MIP. The fact that PaO2 was unchanged despite the fall in PaCO2 suggests that gas exchange may deteriorate with negative pressure ventilation in these patients.

Local cerebral blood flow in spontaneously breathing rats subjected to graded isobaric hypoxia

Local cerebral blood flow (l-CBF) was measured with an autoradiographic technique in spontaneously breathing rats exposed to air or gas mixtures of O2 and N2, giving inspired oxygen fractions (FiO2) ranging from 0.21 to 0.07. The arterial O2 tension (PaO2) changed from 10.9 +/- 0.3 (FiO2 0.21) to 3.9 kPa (FiO2 0.07) (82 +/- 2 to 29 mmHg). Hypoxia caused hyperventilation, and the arterial CO2 tension (PaCO2) fell from 5.21 +/- 0.05 kPa (FiO2 0.21) to 3.27 kPa (FiO2 0.07) (39.1 +/- 0.4 to 24.5 mmHg). The hyperventilatory response was markedly augmented when changing FiO2 from 0.13 to 0.11, causing a fall in PaCO2 of 0.75 kPa and a shift in arterial pH from 7.45 +/- 0.01 (FiO2 0.13) to 7.54 +/- 0.01 (FiO2 0.11). The l-CBF response to hypoxia was found to be biphasic for all the observed regions. At FiO2 0.13, l-CBF was measured about 75% above control but at FiO2 0.11, only 30% above control. A further reduction in FiO2 to 0.07 caused a marked increase in l-CBF, at least 240% of control; however, the applied CBF technique did not admit quantitation. These results suggest that the mechanisms controlling the cerebrovascular response to hypoxia and changes in arterial CO2 tensions are different. The results also indicate that hyperventilation might be harmful to the patient suffering from acute hypoxia.

Safe Intrahospital Transport of Critically III Ventilator-dependent Patients

To determine whether manual ventilation during intrahospital transport of mechanically ventilated critically ill patients results in blood gas and/or hemodynamic abnormalities. A single-blind prospective study evaluated arterial blood gas, blood pressure, heart rate, and arrhythmia changes during mechanical ventilation and manual transport ventilation. University hospital ICUs and various diagnostic or treatment areas. Twenty mechanically ventilated critically ill patients during intrahospital transport. Each patient received mechanical ventilation (MECH) with a volume ventilator while in the ICU and at the study/treatment area. They were manually ventilated (MAN) by a respiratory therapist during transport between areas. The MECH settings were: VT = 0.75 +/- 0.17 L; f = 16 +/- 4; VE = 12.6 +/- 4.3 L/min; FIO2 = 0.46 +/- 0.2. Mean peak Paw = 31 +/- 12 cm H2O and mean effective Cst = 44 +/- 15 ml/cm H2O. No hemodynamic abnormalities were observed. Arterial blood gas values did not vary to any clinically significant degree, except in two patients: one patient had a reduced PaO2 and increased PaCO2 associated with an accidental O2 disconnection and clamped chest tube; another patient had an increased pH by 0.13 units with only a 9 mm Hg fall in PaCO2. Manual ventilation during intrahospital transport of critically ill mechanically ventilated patients is safe provided the person performing manual ventilation knows the inspired oxygen fraction and minute ventilation required before transport and is trained to approximate them during transport.