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Permissive hypercapnia in acute respiratory failure.

OBJECTIVE: To evaluate the potential efficacy of pressure limitation with permissive hypercapnia in the treatment of acute respiratory failure/adult respiratory distress syndrome on the basis of current theories of ventilator-induced lung injury, potential complications of systemic hypercarbia, and available human outcome studies. DATA SOURCES: Articles were identified through MEDLINE, reference citations of published data, and consultation with authorities in their respective fields. STUDY SELECTION: Animal model experimentation and human clinical trials were selected on the basis of whether they addressed the questions of pressure limitation with or without hypercapnia, the pathophysiologic effects of hypercapnia, or the concept of ventilator-induced parenchymal lung injury. Frequently cited references were preferentially included. DATA EXTRACTION: Data were analyzed with particular emphasis on obtaining the following variables from the clinical studies: peak inspiratory pressures, tidal volumes, minute ventilation, and PCO2. Quantitative aspects of respiratory physiology were used to analyze the theoretical effects of permissive hypercapnia on ventilatory requirements in normal and injured lungs. DATA SYNTHESIS: Extensive animal model data support the hypothesis that ventilator-driven alveolar overdistention can induce significant parenchymal lung injury. The heterogeneous nature of lung injury in adult respiratory distress syndrome, with its small physiologic lung volume, may render the lung susceptible to this type of injury through the use of conventional tidal volumes (10 to 15 mL/kg). Permissive hypercapnia is an approach whereby alveolar overdistention is minimized through either pressure or volume limitation, and the potential deleterious consequences of respiratory acidosis are accepted. Uncontrolled human trials of explicit or implicit permissive hypercapnia have demonstrated improved survival in comparison with models of predictive mortality. CONCLUSIONS: Avoidance of alveolar overdistention through pressure or volume limitation has significant support based on animal models and computer simulation. Deleterious effects of the associated hypercarbia in severe lung injury do not appear to be a significant limiting factor in preliminary human clinical trials. Although current uncontrolled studies suggest benefit, controlled trials are urgently needed to confirm these findings before adoption of the treatment can be endorsed.

Acidosis, Respiratory↗

Influence of acidosis on protein metabolism.

Acidosis is a common clinical condition with both chronic and acute forms. Chronic metabolic acidosis induces an increase in protein degradation; however, its effects on protein synthesis are less clear. Metabolic acidosis increases net whole-body proteolysis by a massive increase in protein degradation and only a moderate increase in protein synthesis. Most studies in humans on the relation between acidosis and protein metabolism have concentrated on patients with chronic renal failure with metabolic acidosis. However, because chronic renal failure is associated with other abnormal metabolic conditions such as malnutrition, it is difficult to separate out the effects on protein metabolism solely due to acidosis. Data on the influence of other forms of acidosis, e.g., respiratory acidosis, diabetic ketoacidosis, and lactic acidosis, on protein turnover are sparse. Similarly, data about the influence of acidosis on the metabolism of other proteins, such as the liver-produced secretory proteins, are lacking. Future research should more vigorously investigate the influence of acidosis on protein metabolism in various clinical conditions and the potential regulatory effects on the metabolism of secretory proteins. The reversal of acidosis might prove to have beneficial effects on protein wasting, and thus decrease morbidity and possibly mortality.

Acid-Base Equilibrium↗

[Digoxin level as a limited drug toxicity indicator in the assessment of post-digitalis arrhythmia].

A clinical-laboratory analysis was carried out in 18 patients on long-term treatment with digoxin in whom toxic arrhythmia occurred, taking into account serum digoxin level measurement. In 11 patients the toxic arrhythmia correlated with high digoxin concentration in blood, in six cases it was observed with the concentration of the drug within the therapeutic level range, and in one patient it was seen below this range. Blood digoxin level in patients with hypokalemia was significantly lower in comparison to those with normal serum potassium level. Severe clinical condition of patients, especially elderly persons with hypokalemia, respiratory acidosis and renal failure contributes to the development of toxic arrhythmia; for this reason it is useful to apply in these patients the therapy monitored by blood level of the drug. Electrocardiographic features of digitalis action and non-cardiac adverse effects were seldom observed in patients with toxic arrhythmia.

Acidosis, Respiratory↗

Effects of elevated carbon dioxide environment on calcium metabolism in humans.

BACKGROUND: Chronic respiratory acidosis induced by an elevated carbon dioxide (CO2) environment should provoke hypercalciuria with related total body and subsequent bone calcium losses. We examined this hypothesis in four healthy male volunteers, who were exposed during a 25-d period to an 0.7% CO2 environment within a deep diving isolation chamber. Three months later the same subjects were reexamined during a second campaign being exposed to a 1.2% CO2 atmosphere. METHODS: The subjects received a constant calcium intake (1.4 g.d-1) and vitamin D supplement (1000 IU.d-1) during both campaigns. Calcium balance (oral calcium intake minus urinary and fecal calcium output) was evaluated. Serum calcium concentrations and biomarkers of bone metabolism were measured, in order to evaluate bone turnover. Additionally, the response to an acute oral calcium load was examined as a sensitive measure of changes in calcium metabolism. RESULTS: Both, urinary calcium excretion (from 245 +/- 38 to 199 +/- 31 mg.d-1; mean +/- SE, 0.7% and 1.2%, respectively) and fecal calcium losses (from 1229 +/- 128 to 996 +/- 62 mg.d-1) were significantly reduced in the higher (1.2%) CO2 atmosphere. Although more calcium was retained in the body during the 1.2% than during the 0.7% CO2 campaign, serum calcium concentrations and biomarkers of bone formation were significantly lower in the higher CO2 campaign. Furthermore, bone resorption was slightly increased in the 1.2% experiment. CONCLUSION: Elevated CO2 atmosphere may dose-dependently preserve body calcium without a parallel improvement of bone substance.

Acidosis, Respiratory↗

Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy with special reference to postoperative pain.

To study the possible benefits of N2O pneumoperitoneum, 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were randomized into either CO2-induced (n = 20) or N2O-induced (n = 20) pneumoperitoneum groups. The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale. CO2 insufflation caused respiratory acidosis. The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group (p < 0.041). The N2O group experienced less pain 1 hour (p < 0.040) and 6 hours (p < 0.017) postoperatively and the next morning. Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group. Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2. The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum, especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases.

Acidosis, Respiratory↗

[Management of obesity and respiratory insufficiency. The value of dual-level pressure nasal ventilation].

Obstructive Sleep Apnea (OSA), Obesity-Linked Hypoventilation (OLH)--a hypoventilation which is independent of apneas and increased by sleep--, and COPD are mechanisms for respiratory failure in obese patients. We thought nasal bi-level positive airway pressure to be a suitable treatment: EPAP is useful to maintain upper airway patency and IPAP-EPAP difference to correct OLH and COPD hypoventilation. Our purpose is to report the results of such a therapeutic approach. We included 41 patients that we first treated by nasal bi-level positive airway pressure for a respiratory failure with an uncompensated respiratory acidosis. The initial setting was about 4 cm H2O for EPAP and 16 for IPAP. Under supervision of a real-time printed oximetry tracing, we furthermore increased EPAP until disappearance of repetitive dips in oxygen saturation (that we assimilated to obstructive events) and IPAP until obtaining an acceptable level of steady saturation (we assimilated a low level to a steady hypoventilation). Age (mean +/- SD) was 63 +/- 11 years, BMI 42 +/- 9 kg/m2, pH 7.32 +/- 0.04, PaCO2 71 +/- 13 mmHg, PaO2 45 +/- 7 mmHg. Thirty-nine out of 41 patients returned home without need for tracheal intubation. At 7 days of treatment, PaCO2 was 50 +/- 6 mmHg. Thus, nasal bi-level position airway pressure appears to be an efficient treatment in these patients.

Acidosis, Respiratory↗

Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants.

BACKGROUND: Preterm infants being extubated following a period of intermittent positive pressure ventilation via an endotracheal tube are at risk of developing respiratory failure as a result of apnea, respiratory acidosis and hypoxia. Nasal continuous positive airway pressure appears to stabilise the upper airway, improve lung function and reduce apnea and may therefore have a role in facilitating extubation in this population. OBJECTIVES: In preterm infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV), does management with nasal continuous positive airways pressure (NCPAP) lead to an increased proportion remaining free of additional ventilatory support, compared to extubation directly to headbox oxygen? SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline, previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language and expert informant searches in the Japanese language by Prof. Ogawa. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which NCPAP (delivered by any method) was compared with headbox oxygen for post-extubation care were included. Methodological quality was assessed independently by the two authors. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors. Prespecified subgroup analysis to determine the impact of different levels of NCPAP, differences in duration of IPPV and use of aminophylline were also performed using the same package. MAIN RESULTS: Nasal CPAP, when applied to preterm infants being extubated following IPPV, reduces the incidence of adverse clinical events (apnea, respiratory acidosis and increased oxygen requirements) indicating the need for additional ventilatory support. A reduction in the incidence of chronic lung disease at 28 days of age is also seen in the group extubated to NCPAP. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: nasal CPAP is effective in preventing failure of extubation and reducing oxygen use at 28 days of life in preterm infants following a period of endotracheal intubation and IPPV. Implication for research: further definition of the patient gestational age and weight groups in whom these results apply is required. Optimal levels of NCPAP as well as methods of administration remain to be determined.

Humans↗

Pickwickian syndrome, 20 years later.

The Pickwickian Syndrome stimulated new pathophysiological concepts in regard to control of ventilation. With the advent of sleep laboratories, the peculiar sleep apnea occurring in some of these patients has been explained on the basis of intermittent upper airway obstruction. Two patients with different manifestations of the Pickwickian Syndrome are presented. The suggestion is made that these two subsyndromes should have unique designations. The Auchincloss Syndrome is manifested by right heart failure and respiratory acidosis in obese patients who are alert and have no major abnormality of breathing pattern. The fundamental cause of this abnormality is the increased work of breathing caused by the obesity. The cost of breathing is so high that the ventilatory regulation is compromised and respiratory acidosis results. The Gastaut Syndrome is characterized principally by hypersomnia and sleep apnea. The fundamental defect is upper airway obstruction during sleep, resulting in increased work of breathing, which together with the increased work caused by obesity leads to respiratory acidosis and right ventricular failure. Hypersomnia, rather than heart failure or respiratory acidosis, is the major manifestation of this syndrome, and is the result of sleep loss.

Acidosis, Respiratory↗

Effect of a scorpion (Leiurus quinquestriatus H and E) venom on blood gases and acid-base balance in the rat.

Leiurus quinquestriatus crude venom caused metabolic alkalosis which was partially compensated by respiratory acidosis. Fraction 1 of the venom caused metabolic and respiratory acidosis. The other fractions caused metabolic alkalosis with various degrees of compensation by respiratory acidosis. Fraction 1 caused a marked decrease in blood pH. Hypoxia seemed to be an important contributing factor for this change. Sodium levels decreased while potassium levels increased in the plasma.

Acid-Base Equilibrium↗

Acid-base-electrolyte balance responses of Bufo marinus to aminoglutethimide, corticosterone, and aldosterone during hypercapnia.

Experiments were conducted to test the hypothesis that one or more interrenal steroids are active in regulatory responses to respiratory acidosis in the toad, Bufo marinus. Toads were divided into four experimental groups. The first group received sham injections. The second group received 1-3 mg of aminoglutethimide (AG) every 8 hr. AG inhibits the conversion of cholesterol to pregnenolone, thus inhibiting all steroid hormone synthesis. The third group received AG + 5 micrograms of aldosterone on the same schedule. The fourth group received AG + 25 micrograms of corticosterone on the same schedule as the other groups. All four groups were subjected to hypercapnia using 5% CO2 to induce a respiratory acidosis. The sham-operated animals displayed the normal compensatory pattern of producing a metabolic alkalosis (elevated plasma HCO3-) after 24 hr. AG-treated toads failed to elevate plasma HCO3-. Administration of interrenal steroids produced compensation in varying degrees. Aldosterone produced a small compensation while corticosterone produced a compensation similar to that seen in sham-operated animals. Analysis of steroid titers in toad plasma during hypercapnia showed that Bufo marinus does not elevate aldosterone during respiratory acidosis, but that corticosterone is elevated. AG blocked the corticosterone elevation, however. AG also produced a hyponatremia that was corrected with aldosterone or corticosterone. Normocapnic controls showed that AG does not produce deleterious effects on pH or blood gases in toads in the absence of a respiratory acidosis. We conclude that corticosterone is important in acid-base regulatory responses to respiratory acidosis in this amphibian.

Acid-Base Equilibrium↗

Skeletal muscle lactate release and glycolytic intermediates during hypercapnia.

The effects of respiratory acidosis on glycolysis in the autoperfused canine gastrocnemius-plantaris were studied using anesthetized dogs that were ventilated either with air (n = 30) or with 4% CO2-21% O2-75% N2 (n = 30). The left muscle group was stimulated at 3 Hz for up to 20 min, after which the active and the contralateral resting muscles were removed and frozen in liquid N2. Blood flow, VO2, Vco2, and tension development were unaffected by CO2. Glycogen catabolism was not affected, but lactate release (La) was lower (P less than 0.05) during activity with CO2; and greater fructose 6-phosphate, fructose 6-phosphate/fructose 1,6-diphosphate, and alpha-glycerophosphate/dihydroxyacetone phosphate ratios resulted (P less than 0.05). With respiratory acidosis, muscle lactate tended to accumulate early in contractions, but a net lactate uptake occurred during the last 10 min of contractions. Thus, respiratory acidosis reduced lactate efflux and there was a net uptake late in the contraction period. Glycogen phosphorylase did not appear to be affected by the respiratory acidosis, but there was evidence of inhibition at the phosphofructokinase step as well as a tendency for lactate to accumulate within the muscle. La often occurred in a direction contrary to the muscle-venous lactate concentration difference with either air or CO2 and La also decreased far more rapidly over time than did the arterial-venous H+.

Acidosis, Respiratory↗

Comparison of vecuronium and meperidine on the clinical and metabolic effects of shivering after hypothermic cardiopulmonary bypass.

The use of vecuronium and meperidine on the clinical and metabolic effects of shivering in mechanically ventilated patients after hypothermic cardiopulmonary bypass (CPB) was compared. Twenty adult male patients undergoing cardiac surgery were randomized to meperidine, 25 to 75 mg (n = 10), or vecuronium, 0.1 microgram/kg (n = 10), for the treatment of shivering during postoperative rewarming. Vecuronium was continued as an infusion at 1.0 microgram/kg/min for 4 hours. Meperidine abolished shivering in 50% of patients with a 60% recurrence within 2 hours and did not correct acute respiratory acidosis when it occurred. Vecuronium uniformly abolished shivering, corrected acute respiratory acidosis, and improved mixed venous oxygen saturation (20% v 4%), decreased oxygen consumption (-32% v -7%) and decreased end-tidal carbon dioxide (-21% v -5%) significantly more than meperidine (p < 0.005). Meperidine administration caused a significant decline in systolic blood pressure (121.9 +/- 10.6 mmHg to 106.9 +/- 8.5 mmHg, p = < 0.02). The authors conclude that, during rewarming after hypothermic CPB, muscle relaxation with vecuronium reverses both the clinical and metabolic effects of shivering more reliably and effectively than repeated boluses of meperidine, and with greater hemodynamic stability. Control can be maintained by continuous infusion of vecuronium with concomitant sedation for up to 4 hours without prolonging intubation time.

Acidosis, Respiratory↗

[Laboratory diagnostic monitoring of blood gas parameters in children during bronchologic studies].

Changes in PaO2 and parameters of acid-base-status during bronchological investigations were studied. 20 patients of both sexes with chronic nonspecific respiratory diseases have been investigated. The most important results were a respiratory acidosis after intubation and simultaneous hyperoxigenation during controlled (manual) ventilation. A respiratory acidosis with a small metabolic part was observed during extubation and change to normal respiration. In some cases acidosis was decomposated. These changes were found to be more extensive after bronchography than after bronchoscopy. Acidosis was normalized latest 60 minutes after extubation in all cases. The used method of bronchological examination has caused a favourable influence on the conditions of ventilation.

Acid-Base Equilibrium↗

Helium insufflation in laparoscopic surgery.

Carbon dioxide is the most commonly used gas for abdominal insufflation in laparoscopy today. Due to the solubility of carbon dioxide large volumes are absorbed into the circulation causing a high PCO2 and a low pH (respiratory acidosis). Carbon dioxide is also stored in several sites in the body and is released at the conclusion of the procedure prolonging the respiratory acidosis when the patient is least able to cope with this additional burden. Cardiac effects of CO2 consist of a lowering of the arrhythmia threshold, increased blood pressure, pulse and cardiac output. At a sustained high level this can lead to cardiac depression and death. These effects are particularly prone to occur in cardiac and respiratory cripples. Other gases that have been used include air, oxygen, nitrous oxide and nitrogen. Their use has been discontinued because of the danger of embolism. Air, oxygen and nitrous oxide are also not safe to use in the presence of electrosurgical instruments thereby limiting their usefulness even further. Helium has been proposed as a very promising alternative to CO2. In the laboratory and in a clinical trial, helium has not produced the respiratory acidosis associated with CO2 insufflation. This is further evidence that the acidosis is not primarily due to elevation of the diaphragm and consequent increased dead space, but to the large amount of CO2 that is absorbed directly from the peritoneal cavity. Helium would seem to be the gas of choice at this time as it comes close to fitting the criteria for an ideal insufflating gas. Helium is clear and colorless, allowing unimpeded vision to the operator. It is non toxic, not flammable or explosive and can be safely used with electrocautery and laser. Helium is easy to handle and not very soluble which decreases the amount absorbed from the peritoneal cavity and consequently the amount used. That which is absorbed is quickly cleared by the lungs. Helium is metabolically inactive (in contrast to CO2) and does not interfere with normal metabolic processes. In view of this promising initial work, further studies are indicated.

Abdomen↗

Acid-base disorders: classification and management strategies.

Acid-base disorders are common in clinical practice. Simple acid-base disturbances include metabolic acidosis, metabolic alkalosis, respiratory acidosis and respiratory alkalosis. Each can be clearly identified using a common clinical approach. Proper understanding of acid-base disorders requires knowledge of normal physiology. Each of the simple acid-base disorders can be diagnosed by obtaining a good history and performing a physical examination, followed by determinations of electrolyte levels, anion gap and pH. The degree and nature of compensation should then be analyzed. Finally, the ratio of the change in anion gap to the change in serum bicarbonate (delta AG/delta HCO3-) should be determined. When this diagnostic process is applied, proper identification of the disorder can be made and management can be undertaken. Mixed acid-base disorders can also be identified and managed using this method.

Acid-Base Imbalance↗

The limitations of decision trees and automatic learning in real world medical decision making.

The decision tree approach is one of the most common approaches in automatic learning and decision making. It is popular for its simplicity in constructing, efficient use in decision making and for simple representation, which is easily understood by humans. The automatic learning of decision trees and their use usually show very good results in various "theoretical" environments. The training sets are usually large enough for learning algorithm to construct a hypothesis consistent with the underlying concept. But in real life it is often impossible to find the desired number of training objects for various reasons. The lack of possibilities to measure attribute values, high cost and complexity of such measurements, unavailability of all attributes at the same time are the typical representatives. There are different ways to deal with some of these problems, but in a delicate field of medical decision making, we cannot allow ourselves to make any inaccurate decisions. We have measured the values of 24 attributes before and after the 82 operations of children in age between 2 and 10 years. The aim was to find the dependencies between attribute values and a child's predisposition to acidemia--the decrease of blood's pH. Our main interest was in discovering predisposition to two forms of acidosis, the metabolic acidosis and the respiratory acidosis, which can both have serious effects on child's health. We decided to construct different decision trees from a set of training objects, which was complete (there were no missing attribute values), but on the other hand not large enough to avoid the effect of overfitting. A common approach to evaluation of a decision tree is the use of a test set. In our case we decided that instead of using a test set, we ask medical experts to take a closer look at the generated trees. They examined and evaluated the decision trees branch by branch. Their comments on the generated trees can be found in this paper. The comments show, that trees generated from available training set mainly have surprisingly good branches, but on the other hand some are very "stupid" and no medical explanation could be found. Thereafter we can conclude, that the decision tree concept and automatic learning can be successfully used in real world situations, constrained with the real world limitations, but they should be used only with the guidelines of appropriate medical experts.

Acidosis↗