Respiratory failure

The two principal components of the respiratory system are the lung, which participates in gas exchange, and a muscular pump, which ventilates the lungs (1,2). The ventilatory pump consists of the chest wall (rib cage and abdomen), including the muscles that displace this 

Respiratory failure may be classified as hypoxemic (type 1) or hypercapnic (type II or ventilatory failure) (3), either of which may be acute and chronic. Hypoxemic respiratory failure is due to failure of the lungs, caused by acute (cardiogenic pulmonary edema, pneumonia, acute respiratory distress syndrome) or chronic (emphysema, interstitial limg disorders) diseases (Tables 1 and 2). It is characterized by hypoxemia with normocapnia or hypocapnia. In these conditions central respiratory drive is high and there is sufficient alveolar ventilation (VA) to eliminate CO2 and prevent hypercapnia. 

Hypercapnic respiratory failure is due to failure of the ventilatory pump caused by acute (drug overdose, acute neuromuscular diseases) or chronic (chest wall abnormalities, chronic neuromuscular diseases) disorders. It is characterized by alveolar hypoventilation, which leads to hypercapnia with coexistent, usually mild, hypoxemia. The central drive may be globally reduced with the fall in Pa02 resulting from the increase in alveolar CO2. More commonly, the drive remains high, but the mechanical load on the respiratory systan is too great or the capacity of the muscles too low to ensure efficient CO2 elimination (Fig. 1). 

In individual patients, however, both types of respiratory failure may coexist, as one respiratory problem leads to another with a cascade of interaction (3). For example, patients with cardiogenic pulmonary edema or status asthmaticus first develop hypoxemia due to lung failure if the disease persists or progresses, pump failure and hypercapnia appear because of several mechanisms (increased work of breathing, reduced oxygen delivery, hyperinflation). 

Respiratory failure can develop over minutes to hours (acute respiratory failure) or over several days or longer (chronic respiratory failure). The distinction between acute and 

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Manufacture, Shipment, and Analysis. In the United States, sodium and potassium thiocyanates are made by adding caustic soda or potash to ammonium thiocyanate, followed by evaporation of the ammonia and water. The products are sold either as 50—55 wt % aqueous solutions, in the case of sodium thiocyanate, or as the crystalline soHds with one grade containing 5 wt % water and a higher assay grade containing a maximum of 2 wt % water. In Europe, the thiocyanates may be made by direct sulfurization of the corresponding cyanide. The acute LD q (rat, oral) of sodium thiocyanate is 764 mg/kg, accompanied by convulsions and respiratory failure LD q (mouse, oral) is 362 mg/kg. The lowest pubhshed toxic dose for potassium thiocyanate is 80—428 mg/kg, with hallucinations, convulsions, or muscular weakness. The acute LD q (rat, oral) for potassium thiocyanate is 854 mg/kg, with convulsions and respiratory failure. 

Nickel carbonyl Carbonylation of acetylene and alcohols to produce acrylic and methacrylic acids Acute respiratory failure carcinogenic... 

PuAEMACoLOGiCAL AcTiox. Curare is stated to be almost inert when taken by mouth, owing to poor absorption by intestinal mucous membrane and the rapidity of elimination. Injected hypodermically it is a rapid and potent poison, paralysing the motor nerve-endings in striped muscle, so that voluntary movements cease and death occurs from respiratory failure. 

Both Cushny and Dale found the amorphous gelsemium alkaloids represented by such fractions as gelseminine much more active than gelsemine. Cushny stated that gelseminine resembled coniine in action and showed a greater depressant effect on the central nervous system, but unlike coniine it exerted no pressor effect. It was also a powerful mydriatic. Dale found that 0-001 gm. of the hydrochlorides of the amorphous alkaloids injected into rabbits caused death from respiratory failure in 25 minutes, preceded by convulsions. These results are explained by the subsequent isolation from such amorphous fractions, of the potent alkaloids sempervirine and gelsemicine. 

Botulism is a disease caused by ingestion of foods contaminated with Clostridium botulinum (food-borne botulism) or, very rarely, by wound infection (wound botulism) or colonization of the intestinal tract with Clostridium botulinum (infant botulism). The toxins block the release of acetylcholine. Botulism is characterized by generalized muscular weakness, which first affects eye and throat muscles and later extends to all skeletal muscles. Flaccid paralysis can lead to respiratory failure. 

Mice homozygous for an ETA receptor gene disruption show craniofacial malformations, such as cleft palate, micrognathia, microtia and microglossia. ETA (—/—) mice die shortly after birth due to respiratory failure. Mice with an ET-l-null mutation show the same cranciofacial malformations and, in addition, cardiovascular disorders (e.g. septal defects, abnormal cardial outflow tract, aortic arch and subclavian arteries). 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

The severe X-linked form of centronuclear myopathy is often associated with reduced fetal movement and hydramnios, and may be fatal in the neonatal period due to respiratory failure. Children may survive for several years but often only with assisted ventilation. In only a few reported cases has the condition allowed any form of active life. Female relatives may show a carrier state characterized by the presence of some small myotubelike type 1 fibers in an otherwise normal muscle fiber population. 

The lethal dose of mescaline varies because of the development of tolerance to the action of the drug. After a massive overdose, hypotension, bradycardia, CNS depression, and respiratory failure may be life threatening. Fatal intoxications from mescaline are rare, and fatalities associated with mescaline use are usually attributed to traumas resulting from altered perceptions. 

The effects of protein deficiency on endosulfan toxicity were studied in Wistar rats (Boyd and Dobos 1969 Boyd et al. 1970). Rats fed a diet totally deficient in protein for 28 days prior to administration of a single oral dose of endosulfan had an LDjq of 5.1 mg/kg of endosulfan. Rats fed a low-protein diet (3.5% protein) for 28 days had an LDjq of 24 mg/kg of endosulfan. Rats fed standard laboratory chow (26% protein) had an LDjq of 102-121 mg/kg. The immediate cause of death in all animals was respiratory failure following tonic-clonic convulsions. This study demonstrated that, while a protein-deficient diet does not affect the nature of the toxic reaction, it may affect the sensitivity of rats to the lethal effects of endosulfan. 

A related organism, CL botulinum, produces a similar toxin which may contaminate food if the organism has grown in it and conditions are favourable for anaerobic growth. Meat pastes and pates are likely sources. This toxin interferes with acetylcholine release at cholinergic syrrapses and also acts at neuromuscular jimctions. Death fiom this toxin eventually results firm respiratory failure. 

Sznadjer, J.I., Fraiman, A. and Hall, J.B. (1989). Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure. Chest 96, 606-612. 

Age >40 yr, previous venous thromboembolism, chronic heart failure, acute respiratory failure, recent major surgery (within 2 wk), confined air/ground travel (>6 h duration within 1 wk of admission), inflammatory bowel disease, myocardial infarction, nephrotic syndrome, and ischemic stroke... 

FEVj < 30% or presence of chronic respiratory failure or right heart failure... 

Add long-term oxygen therapy if chronic respiratory failure ° Consider surgical treatments... 

Mental status changes may indicate impending respiratory failure. 

In patients with severe exacerbations, monitoring of Pco2 should be considered. Patients with acute asthma usually have a respiratory alkalosis, and a normal or increased Pco2 indicates the potential for respiratory failure. 

Perform a brief medical history to determine the time of symptom onset, symptom severity, symptom severity in relation to previous exacerbations, current medications, previous emergency department visits or hospitalizations due to asthma, previous history of respiratory failure, and psychiatric or psychological disorders. 

IV Very severe Long-term oxygen if chronic respiratory failure... 

Long-term administration of oxygen (greater than 15 hours per day) to patients with chronic respiratory failure has been shown to reduce mortality and improve quality of life.1,2 Oxygen therapy should be initiated in stable patients with very severe COPD (GOLD stage IV) who are optimized on... 

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