Chronic obstructive pulmonary disease and sleep

The control of breathing in patients with chronic obstructive pulmonary disease (COPD) follows the same basic principles as in normal subjects, both awake and asleep, with an expected lower feedback response during sleep. This impacts nocturnal gas exchange and sleep quality most profoundly in patients with more severe COPD, as multiple factors come into play. Hypoventilation causes the most important gas-exchange alteration in COPD patients, leading to hypercapnia and hypoxemia, especially during rapid-eye-movement sleep, when marked respiratory muscle atonia occurs. The hypoxia leads to increased arousals, sleep disruption, pulmonary hypertension, and higher mortality. The primary mechanisms for this include decreased ventilatory responsiveness to hypercapnia, reduced respiratory muscle output, and marked increases in upper airway resistance. In the presence of more profound daytime hypercapnia, polysomnography should be considered (over nocturnal pulse oximetry) to rule out other co-existing sleep-related breathing disorders such as obstructive sleep apnea (overlap syndrome) and obesity hypoventilation syndrome. Present consensus guidelines provide insight into the proper use of oxygen, continuous positive airway pressure, and nocturnal noninvasive positive-pressure ventilation for those conditions, but several issues remain contentious. In order to provide optimal therapy to patients, the clinician must take into account certain reimbursement and implementation-process obstacles and the guidelines for treatment and coverage criteria.     

Oxygen therapy and exercise response in lung disease

Lung disease affects exercise performance through a number of mechanisms, including hypoxemia, abnormal ventilatory mechanics, abnormal ventilatory muscles, abnormal ventilatory patterns, abnormal right heart function and subjective dyspnea. Supplemental oxygen improves hypoxemia and thus improves exercise impairment resulting from hypoxemia-related reductions in oxygen delivery. Supplemental oxygen also reduces exercise ventilation. This, in turn, reduces ventilatory muscle work, and the concomitant permissive hypercapnia may have beneficial effects at the cellular level. Additionally, in obstructive disease patients, an improved ventilatory pattern may reduce air trapping. Supplemental oxygen may also improve right ventricular dysfunction in patients with underlying right ventricular dysfunction. Finally, supplemental oxygen may reduce dyspnea caused by oxygen-related carotid body activity. Important questions remain. First, is long-term oxygen use of benefit in patients with only exercise hypoxemia? Second, is exercise conditioning possible in patients with exercise hypoxemia? Third, does supplemental oxygen enhance exercise conditioning efforts in those patients with CLD but without exercise hypoxemia? If the answer to this last question is yes, what selection criteria should be used to identify those who would benefit? The answers to all of these questions will have enormous impact on our approach to the optimal management of CLD patients.     

The ability of pulse oximetry to screen for hypoxemia and hypercapnia in patients breathing room air

This study was designed to determine whether high room-air pulse oximetry can rule out hypoxemia or moderate hypercapnia. Based on retrospective analysis of 513 arterial blood gas results, oxygen saturation cutpoints were derived. Coincidentally, a room-air oxygen saturation (RAO₂ sat) value of 96% was selected as a cutpoint to screen for both hypoxemia (PaO₂ < 70 mm Hg) and moderate hypercapnia (PaCO₂ > 50 mm Hg). These tests were validated prospectively by using a convenience sample of 213 Emergency Department patients in whom room-air arterial blood gas sampling was ordered. To detect hypoxemia, the sensitivity of RAO₂ sat ≤ 96% was 1.0 [0.95–1.0, 95% confidence interval (CI)] and specificity was 0.54 (0.45–0.64, 95% CI). To detect hypercapnia, the sensitivity of RAO₂ sat ≤ 96% was 1.0 (0.7–1.0) and specificity was 0.31 (0.25–0.38, 95% CI). We concluded that RAO₂ sat ≥ 97% rules out hypoxemia and may also rule out moderate hypercapnia.     

The technique of instituting mechanical ventilation. Patient preparation; endotracheal intubation; monitoring

Potential indications for mechanical ventilation include hypoxemia unresponsive to oxygen administration, hypercapnia resulting in acidemia, and an unstable chest wall. For best results, carefully prepare the patient (both physically and emotionally) before instituting ventilation. Sedatives and local anesthesia can facilitate intubation; avoid paralytic agents unless you are experienced at intubation. The oral route is most commonly used. Once the patient circuit is attached to the endotracheal tube, reexamine the patient and double-check the inspiratory flow and I:E ratio; adjust the ventilator's settings as necessary. Monitor the patient frequently to ascertain the adequacy of alveolar ventilation and arterial oxygen.     

Furosemide pharmacodynamics: effect of respiratory and acid-base disturbances

The aims of this study were to investigate the effect of changes in arterial blood gases and pH on furosemide pharmacodynamics and kinetics. Five groups of conscious rabbits were used: a control group breathing air with normoxia and normocarbia; a second group with hypercapnia and respiratory acidosis; a third with hypoxemia; a fourth with hypercapnia and respiratory acidosis combined with hypoxemia (HCHO); and the fifth group with metabolic acidosis. All experimental conditions, except hypoxemia, increased sodium tubular reabsorption and therefore, decreased urinary excretion of sodium. Renal blood flow was decreased by HCHO and metabolic acidosis. In response to 5 mg/kv i.v. of furosemide, natriuresis and diuresis were decreased by an average of 44% in animals with HCHO (P less than .05). The kinetics of furosemide were not affected by any of the experimental conditions except HCHO, in which the renal clearance of furosemide was reduced from 7.5 +/- 1.4 ml/min/kg (controls) to 2.7 +/- 0.7 ml/min/kg (P less than .05). The reduction in renal clearance of furosemide was associated with a decrease in urinary excretion of sodium (P less than .05). The reduction in renal clearance of furosemide was probably secondary to the decrease in renal blood flow and an increase in furosemide tubular reabsorption. Finally, HCHO did not decrease plasma volume, suggesting that the reduction in renal blood flow was secondary to blood flow distribution. In conclusion, only hypercapnia and respiratory acidosis combined with hypoxemia decreases the natriuretic and diuretic effect of furosemide.     

Respiratory acidosis

Respiratory acidosis, or primary hypercapnia, is the acid-base disorder that results from an increase in arterial partial pressure of carbon dioxide. Acute respiratory acidosis occurs with acute (Type II) respiratory failure, which can result from any sudden respiratory parenchymal (eg, pulmonary edema), airways (eg, chronic obstructive pulmonary disease or asthma), pleural, chest wall, neuromuscular (eg, spinal cord injury), or central nervous system event (eg, drug overdose). Chronic respiratory acidosis can result from numerous processes and is typified by a sustained increase in arterial partial pressure of carbon dioxide, resulting in renal adaptation, and a more marked increase in plasma bicarbonate. Mechanisms of respiratory acidosis include increased carbon dioxide production, alveolar hypoventilation, abnormal respiratory drive, abnormalities of the chest wall and respiratory muscles, and increased dead space. Although the symptoms, signs, and physiologic consequences of respiratory acidosis are numerous, the principal effects are on the central nervous and cardiovascular systems. Treatment for respiratory acidosis may include invasive or noninvasive ventilatory support and specific medical therapies directed at the underlying pathophysiology.     

Pulmonary extraction of propranolol in normal and oxygen-toxic sheep

To help define the mechanisms involved in the handling of propranolol by normal and injured lungs, we studied the pulmonary extraction of [3H]propranolol in 23 unanesthetized sheep. Extraction of propranolol by normal lungs during a single circulation was characterized by 1) subsequent back-diffusion and pulmonary retention of the drug, 2) no evidence of saturable uptake or binding, 3) no effect of isoproterenol or imipramine, and 4) no effect of increasing cardiac output by treadmill exercise. In lungs damaged by oxygen toxicity, [3H]propranolol extraction decreased progressively to 63% of base line, paralleling progressive arterial hypoxemia and hypercapnia. In contrast, [14C]serotonin extraction remained unchanged from base line. Our results suggest that in normal unanesthetized sheep, pulmonary extraction of propranolol occurs primarily by passive diffusion that is flow-limited. Also, lung injury induced by oxygen toxicity in sheep reduces the pulmonary extraction of propranolol. Indeed, in oxygen toxicity, the depressed extraction of propranolol is a more sensitive marker of lung injury than is serotonin extraction.     

The Effects of Chronic Hypoxemia on Electrolyte and Acid—Base Equilibrium: An Examination of Normocapneic Hypoxemia and of the Influence of Hypoxemia on the Adaptation to Chronic Hypercapnia

We have carried out balance studies in normal dogs in order to appraise the effects of chronic hypoxemia on acid-base and electrolyte equilibrium. During the first phase of observation we produced a state of "pure" hypoxemia by reducing the oxygen concentration (utilizing nitrogen as a diluent) and by adding carbon dioxide to the environment in a concentration sufficient to keep arterial CO(2) tension (PCO(2)) within normal limits. The data demonstrate that such a 9-day period of normocapneic hypoxemia has no effect on electrolyte excretion and is virtually without effect on plasma composition.During the second phase of observation we subjected the hypoxemic dogs to stepwise increments in arterial carbon dioxide tension in order to evaluate the effects of the low oxygen tension on the acid-base adjustments to a chronic state of hypercapnia. At least 6 days was allowed for extracellular composition to reach a new steady state at each level of inspired carbon dioxide. The data demonstrate a rise in both plasma bicarbonate concentration and renal acid excretion that was not significantly different from that which has been described previously for hypercapnia without hypoxemia. Just as in these earlier studies, plasma hydrogen ion concentration rose with each increment in carbon dioxide tension, each millimeter Hg increment in PCO(2) leading to an increase in hydrogen ion concentration of 0.32 nmole per L. It thus appears that the chronic"carbon dioxide response curve" is not significantly influenced by moderately severe hypoxemia.     

Aspiration of dead space in the management of chronic obstructive pulmonary disease patients with respiratory failure

INTRODUCTION: Carbon dioxide clearance can be improved by reducing respiratory dead space or by increasing the clearance of carbon-dioxide-laden expiratory gas from the dead space. Aspiration of dead space (ASPIDS) improves carbon dioxide clearance by suctioning out (during expiration) the carbon-dioxide-rich expiratory gas while replacing the suctioned-out gas with oxygenated gas. We hypothesized that ASPIDS would allow lower tidal volume and thus reduce exposure to potentially injurious airway pressures. METHODS: With 8 hemodynamically stable, normothermic, ventilated patients suffering severe chronic obstructive pulmonary disease we tested the dead-space-clearance effects of ASPIDS. We compared ASPIDS to phasic tracheal gas insufflation (PTGI) during conventional mechanical ventilation and during permissive hypercapnia, which was induced by decreasing tidal volume by 30%. The mean P(aCO(2)) reductions with PTGI flows of 4.0 and 6.0 L/min and during ASPIDS (at 4.0 L/min) were 32.7%, 51.8%, and 53.5%, respectively. Peak, plateau, and mean airway pressure during permissive hypercapnia were significantly lower than during conventional mechanical ventilation but PTGI increased peak, plateau, and mean airway pressure. However, pressures were decreased during permissive hypercapnia while applying ASPIDS. Intrinsic positive end-expiratory pressure also increased with PTGI, but ASPIDS had no obvious influence on intrinsic positive end-expiratory pressure. ASPIDS had no effect on cardiovascular status. CONCLUSIONS: ASPIDS is a simple adjunct to mechanical ventilation that can decrease P(aCO(2)) during conventional mechanical ventilation and permissive hypercapnia.     

Persistent hypercapnia in children after treatment of obstructive sleep apnea syndrome by adenotonsillectomy

Obstructive sleep apnea syndrome (OSAS) in childhood is frequently in part a consequence of enlarged adenoids and/or tonsils and may lead to hypoxemia and hypercapnia during sleep. Whereas long-term blood gas alterations are well documented in adults, only few polygraphic data are available for children. It was the aim of this study to document blood gas alterations before and after treatment in this population. 9 children with OSAS (6 male, 3 female, median age 5.9 years, range 1.1-13.5 years) were investigated by polysomnography before and after adenotonsillectomy. Prior to intervention most children presented with moderate hypercapnia (ETCO2 mean 44.3 +/- 3.8 mm Hg, ETCO2 maximum 53.2 +/- 5.2) and hypoxemic episodes (oxygen saturation mean 93.2 +/- 3.2%, minimum 74.4 +/- 16.5%). Following adenotonsillectomy subsequent polygraphic investigations displayed normalisation of oxygen saturation (saturation mean 96.1 +/- 0.8%, minimum 90.1 +/- 3.1%). In contrast, moderate hypercapnia in several patients persisted up to five months after treatment (ETCO2 mean 44.9 +/- 2.8 mm Hg, ETCO2 maximum 51.2 +/- 3.6). Persistent hypercapnia most likely reflects an adaptation process of chemosensitivity and respiratory control due to preceding long-term hypercapnia.     

静脉输氧技术治疗感染性疾病严重低氧血症的探讨

目的　探讨纠正感染性疾病患者严重低氧血症的给氧新方法。方法　将高浓度氧气溶解在常规输液用液体内制备成为高氧液 ,通过静脉输液的方式进行输氧。对 6例严重急性呼吸综合征 (SARS)和 3例艾滋病患者每日静脉滴注高氧液 5 0 0～ 70 0 m l,疗程 1～ 5 d。观察治疗前后患者的临床症状及血氧指标变化。结果　在静脉输注高氧液 2 0 min～ 4 h后 ,9例患者的缺氧症状均缓解 ,呼吸由 2 9～ 4 9次 / min降为 18～2 2次 / m in,心率由 89～ 14 5次 / m in降为 6 0～ 79次 / min,2例昏迷患者意识转清。低氧血症逐渐恢复正常 ,动脉血氧分压 (Pa O2 )由平均 5 6 m m Hg(1mm Hg=0 .133k Pa)变为 87m m Hg;动脉血氧饱和度 (Sa O2 )由平均0 .89变为 0 .96。结论　对 SARS和艾滋病等感染性疾病患者的低氧血症 ,常规气道供氧有时难以奏效 ;静脉输氧能够迅速提高 Pa O2 ,可作为感染性疾病严重低氧血症的综合治疗措施之一 ;尤其是静脉输氧绕过了SARS患者弥散功能障碍的肺泡 ,有助于此类患者的抢救。     

Impaired Reflex Vasoconstriction in Chronically Hypoxemic Patients

Acute hypoxia impairs vasoconstrictor responses in normal men. The present study was done to determine whether reflex vasoconstriction is impaired in chronically hypoxemic patients and whether correction of hypoxemia in these patients improves their cardiovascular reflexes. In eight chronically hypoxemic patients, arterial P(O2) was increased from an average of 45 mm Hg while breathing room air to 161 mm Hg while breathing 40-100% oxygen, with minimal changes in arterial P(CO2) or pH. Correction of hypoxemia did not cause changes in resting arterial pressure or in forearm vascular resistance, but it caused a small increase in resting heart rate. Reflex responses to lower body negative pressure, which causes pooling of blood in the lower part of the body, were observed. When the patients were hypoxemic, lower body negative pressure caused a fall in arterial pressure, slight constriction of forearm vessels, and a small increase in heart rate. When hypoxemia was corrected, the same intervention caused marked vasoconstriction and a greater increase in heart rate, and there was no decrease in arterial pressure. The results indicate that reflex vasoconstrictor responses are depressed in chronic hypoxemia, indicating that adaptive mechanisms which occur in chronic hypoxemia do not include preservation of sympathetic reflexes.     

Ventilation-perfusion lung imaging in diaphragmatic paralysis.

We have described a patient with paralysis of the diaphragm, in whom dyspnea, hypoxemia, and hypercapnia increased when he changed from the upright to the supine position. Ventilation (V) and perfusion (P) images of the right lung appeared to be normal and remained nearly the same in the upright and supine positions. In contrast, V and P images of the left lung were smaller than those of the right lung in the upright position and decreased further in the supine position. In addition, the ventilation image of the left lung was much smaller than the perfusion image in both positions.     

Mechanisms producing hypoxemia during hemodialysis

Arterial hypoxemia occurs frequently during hemodialysis. Proposed mechanisms for this phenomenon have included hypoventilation and embolism of granulocyte aggregates. We studied 18 patients with endstage renal failure who required chronic hemodialysis, and measured arterial blood gases, pulmonary gas exchange, and dialyzer gas exchange. During use of acetate as a dialysate buffer, PaO2 decreased to 80 +/- 6.8 torr, whereas during use of the bicarbonate buffer oxygen tension remained at 92 +/- 4.9 torr or greater. Hypoventilation and microembolism were not sufficient to explain the degree of hypoxemia during acetate dialysis. Hypoxemia occurred only after the 1st exposure to acetate; neither an instantaneous change to bicarbonate nor stopping dialysis restored oxygen tension to normal. We conclude that a pharmacologic action of acetate adversely affects lung function, aggravating the decreased alveolar oxygen tension (PAO2) due to hypoventilation. Hypoxemia was not present when bicarbonate was used. Acetate buffer should not be used for dialysis in patients with unstable cardiovascular or respiratory systems.     

Mechanisms of gas exchange abnormality in patients with chronic obliterative pulmonary vascular disease.

We have examined the mechanisms of abnormal gas exchange in seven patients with chronic obliteration of the pulmonary vascular bed secondary to recurrent pulmonary emboli or idiopathic pulmonary hypertension. All of the patients had a widened alveolar-arterial oxygen gradient and four were significantly hypoxemic with arterial partial presssures of oxygen less than 80 torr. Using the technique of multiple inert gas elimination, we found that ventilation-perfusion (VA/Q) relationships were only minimally abnormal with a mean of 10% (range, 2--19%) of cardiac output perfusing abnormal units. These units consisted of shunt and units with VA/Q ratios less than 0.1. In addition, the dead space was found to be normal in each patient. There was no evidence for diffusion impairment, and the widened alveolar-arterial oxygen gradient was completely explained by VA/ inequality. Significant hypoxemia occurred only when VA/Q inequality was combined with a low mixed venous oxygen content.     

Oxygen-carrying capacity during 10 hours of hypercapnia in ventilated dogs

OBJECTIVE: To test if a relatively long-term exogenous hypercapnia, equivalent to those maintained during permissive hypercapnia, can persistently increase oxygen-carrying capacity in ventilated dogs. DESIGN: Prospective study. SETTING: Research laboratory in a hospital. SUBJECTS: Six mongrel dogs (3 males; 3 females). INTERVENTIONS: The dogs were anesthetized (30 mg/kg pentobarbital, i.v.), intubated, and cannulated in one femoral artery, one femoral vein, and the right jugular vein. The mean arterial blood pressure, heart rate, and mean pulmonary artery pressure were continuously recorded. Anesthesia, fluid balance, and normothermia were maintained. Arterial hypercapnia was generated by the addition of 60 torr dry CO2 (8 kPa) to the inspired air for 10 hrs, continuously. All subjects were paralyzed (vecuronium bromide) and ventilated with room air, while the ventilator settings were kept constant. MEASUREMENTS AND MAIN RESULTS: Arterial and venous gas exchange profiles, hemoglobin concentration, oxygen saturation, oxygen content, cardiac output, and oxygen consumption were determined, before, during, and after 10 hrs of hypercapnia, periodically. Both hemoglobin concentration and oxygen content were gradually increased during hypercapnia and reached significant levels at 8 and 10 hrs of hypercapnia, respectively. These increases continued up to 2 hrs after termination of hypercapnia. The PaO2/FIO2, as an index of arterial oxygenation, was significantly increased during the first 3 hrs of hypercapnia and then remained at the normoxic level up to 10 hrs of hypercapnia. No significant changes occurred in the mean arterial blood pressure and oxygen consumption. The heart rate and cardiac output were significantly reduced at 4 and 8 hrs of hypercapnia, respectively. The mean pulmonary artery pressure was increased throughout the hypercapnic trial. CONCLUSIONS: A relatively long-term exogenous hypercapnia can significantly increase oxygen-carrying capacity in normal ventilated dogs. Whether this effect can occur during permissive hypercapnia because of controlled ventilation in patients warrants investigation.     

Abdominal fat and sleep apnea: the chicken or the egg?

Obstructive sleep apnea (OSA) syndrome is a disorder characterized by repetitive episodes of upper airway obstruction that occur during sleep. Associated features include loud snoring, fragmented sleep, repetitive hypoxemia/hypercapnia, daytime sleepiness, and cardiovascular complications. The prevalence of OSA is 2-3% and 4-5% in middle-aged women and men, respectively. The prevalence of OSA among obese patients exceeds 30%, reaching as high as 50-98% in the morbidly obese population. Obesity is probably the most important risk factor for the development of OSA. Some 60-90% of adults with OSA are overweight, and the relative risk of OSA in obesity (BMI >29 kg/m(2)) is >or=10. Numerous studies have shown the development or worsening of OSA with increasing weight, as opposed to substantial improvement with weight reduction. There are several mechanisms responsible for the increased risk of OSA with obesity. These include reduced pharyngeal lumen size due to fatty tissue within the airway or in its lateral walls, decreased upper airway muscle protective force due to fatty deposits in the muscle, and reduced upper airway size secondary to mass effect of the large abdomen on the chest wall and tracheal traction. These mechanisms emphasize the great importance of fat accumulated in the abdomen and neck regions compared with the peripheral one. It is the abdomen much more than the thighs that affect the upper airway size and function. Hence, obesity is associated with increased upper airway collapsibility (even in nonapneic subjects), with dramatic improvement after weight reduction. Conversely, OSA may itself predispose individuals to worsening obesity because of sleep deprivation, daytime somnolence, and disrupted metabolism. OSA is associated with increased sympathetic activation, sleep fragmentation, ineffective sleep, and insulin resistance, potentially leading to diabetes and aggravation of obesity. Furthermore, OSA may be associated with changes in leptin, ghrelin, and orexin levels; increased appetite and caloric intake; and again exacerbating obesity. Thus, it appears that obesity and OSA form a vicious cycle where each results in worsening of the other.     

肾移植后的重症肺炎

背景：肾移植后重症肺炎发生率高,死亡率高,对其进行早期诊断及治疗具有重要意义。目的：分析呼吸重症监护室收治的肾移植后重症肺炎患者的临床特点、病情及预后,以提高其早期诊断率及治愈率。方法：对2004年1月至2012年9月郑州人民医院呼吸重症监护室收治的28例肾移植后出现重症肺炎的患者进行回顾性调查分析,总结其临床特点。应用急性生理学与慢性健康状况评分Ⅱ、英国胸科协会改良肺炎评分对患者病情进行评估,并给予适当的治疗。结果与结论：28例患者重症肺炎感染发生在肾移植后3-8个月,普遍应用免疫抑制剂的剂量较大;主诉有呼吸急促、干咳、胸闷、发热。血浆白蛋白下降明显,动脉血气分析均为低氧血症,低二氧化碳血症,动脉血氧饱和度进行性下降。胸部CT示肺部广泛渗出阴影。停用免疫抑制药物,并给予广谱抗感染药物、甲基泼尼松龙及无创呼吸机治疗后,治愈24例、好转2例、死亡2例。治疗期间患者肝、肾功能无恶化。提示肾移植后免疫抑制过度是并发重症肺炎的高危因素;重视体温监测,活动后气促及不明原因血清白蛋白下降有助于早期诊断。果断停用免疫抑制剂,并进行抗感染、甲基泼尼松龙及恰当无创呼吸机治疗是治疗成功的关键。     

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

OBJECTIVE: 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. DESIGN: Animal studies, using the newborn lamb, with comparison to control group. SUBJECTS: 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). SETTING: Work was conducted in the research laboratories at Children's National Medical Center, Washington, DC. INTERVENTIONS: 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. MEASUREMENTS: 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. MAIN RESULTS: 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. CONCLUSIONS: 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.     

Acute dyspnea--what should I not forget?

Acute dyspnea represents a diagnostic challenge even for the experienced physician. There are no prospectively evaluated diagnostic algorithms dealing with this frequent clinical problem. First of all, the emergency has to be assessed and life supporting measures have to be considered. In addition to a thorough medical history and clinical examination, chest X-ray, spirometry, ECG, hemoglobin measurement, BNP and D-dimer testing represent valuable diagnostic tools and are available to GP's. Most commonly, acute dyspnoea is pulmonary or cardiac in origin. Up to one third of all cases will have several causes. Functional dyspnea is difficult to diagnose but should be taken into consideration after excluding any somatic cause. Hyperventilation is found in both, organic and non organic diseases, and is therefore an inappropriate criterion to differentiate between the two. The mainstay in the management of any symptom is to primarily treat the underlying disease. A significant hypoxemia (SO2 < 90%, pO2 < 60 mmHg) ought to be corrected by supplemental oxygen. It is inappropriate to withhold oxygen from patients with COPD and severe hypoxemia just to avoid hypercapnia. Besides oxygen, opiates efficiently relief dyspnoea but harbour the risk of respiratory depression, altered mental status or aspiration.