Oxygen therapy

Hypoxia is a reduction in the total content of oxygen (CaO₂) in arterial blood. It can be caused by:

• hypoventilation
• ventilation-perfusion mismatch
• diffusion deficit
• cardiac shunts
• intrapulmonary shunts
• decrease in the fraction of inspired oxygen (FiO₂).

Pathologic conditions affecting the pulmonary parenchyma, the neuromuscular activity, the pleural cavity, the chest wall and certain heart conditions can be the cause of the above mentioned deficits. CaO₂ is the measurement of all the oxygen present in the blood. It is calculated by summing the oxygen component deriving from the pressure gradient and the oxygen component bound to haemoglobin, as indicated in the formula:

CaO₂ = (1.3 x Hb x SaO₂) + (0.003 x paO₂)                           (1)

Legend: Hb = haemoglobin (g/dl), SaO₂ = saturation of haemoglobin in arterial blood (n/100), PaO₂ (mmHg)

Formula nr. 1 shows how CaO₂ is influenced by the haemoglobin content compared to the amount of oxygen present in the blood by pressure gradient; in fact, the amount of oxygen bound to haemoglobin is about 40 times greater than the amount of oxygen dissolved in the blood (PaO₂). In patients with hypoxia, the amount of haemoglobin should be tested and restored as early as possible because a reduction in CaO₂, which also causes a reduction in the availability of oxygen (DO₂), increases the risk of shock and mortality in critically ill patients.^_1,2

As an example, if in an hypoxic patient a 50% haemoglobin reduction is present (e.g. due to haemorrhage), the CaO₂ value will be of about 9 ml/dl, when in a normal patient it is of about 19-21 ml/dl; if such patient is supplied with 100% oxygen nasally, the CaO₂ will be at 9.8, while if a 20 ml/kg blood transfusion is given, even without administering oxygen, the CaO₂ will increase to about 13 ml/dl. A severe reduction in CaO₂ can trigger an anaerobic cell metabolism, with the formation of lactic acid in excess. The reduced production of energy resulting from anaerobiosis (from 1 mole of glucose only 2 moles of ATP are obtained, instead of 36) (Fig. 1), if severe and prolonged over time, can cause decompensated metabolic acidosis and cell death.

Fig. 1. ATP production in aerobic and anaerobic metabolism

Hypoxia can be very serious and should always be suspected in the following diseases:

• SIRS (systemic inflammatory response syndrome), sepsis, severe sepsis, septic shock   
• anaemia
• anterograde and retrograde heart failure
• head trauma
• metabolic acidosis
• metabolic alkalosis
• respiratory alkalosis or acidosis.

Oxygen therapy is effective in the presence of reduced oxygenation (quantified by measuring PaO₂); when the respiratory distress is instead caused by a ventilation deficit (increase of PaCO^₂) oxygen therapy is not very effective. It is necessary to remember that a ventilation deficit can also cause hypoxia, and in these cases oxygen can make the difference between life and death. In view of the fact that it is not possible to know in advance which patients, with impaired ventilation that is incompatible with life, may survive thanks to oxygen therapy, the use of oxygen is recommended even in the course of respiratory distress of ventilatory origin, until the pathologic condition has been resolved (e.g. pneumothorax). By increasing FiO₂ (fraction of inspired oxygen that in ambient air is 21%), oxygen therapy increases the partial pressure of oxygen at the alveolar level and the diffusion of oxygen from the alveoli to the pulmonary capillaries.

DIAGNOSIS OF HYPOXIA

In order to diagnose hypoxia a blood-gas analysis is needed, possibly an arterial blood-gas analysis. In its absence, the evaluation of haemoglobin saturation can also provide indications about the state of oxygenation (Table 1). In fact, the dissociation curve of haemoglobin is an indication of PaO₂ (Fig. 2).

Table 1. Oxygenation and pulse oximetry

Fig. 2. Haemoglobin dissociation curve

Legend: SaO₂%: percentage of haemoglobin saturation, PaO₂: partial arterial oxygen pressure, T°: body temperature, PaCO₂: partial arterial pressure of carbon dioxide, 2-3DPG: 2-3 diphosphoglycerate.

To diagnose whether respiratory distress is caused or not by a ventilation deficit it is necessary to quantify PaCO₂ (partial pressure of arterial carbon dioxide). PaCO₂ can be measured by arterial blood-gas analysis or by evaluating CO₂ at the end of expiration (TCO₂) with a capnograph. Microstream capnographs, equipped with a nasal probe, can also be used in conscious patients, as they do not require endotracheal intubation. The ventilation deficit may be caused by:

• pleural space diseases
• lower airway obstruction
• hypoventilation
• neuromuscular diseases
• increased alveolar dead space.

OXYGEN THERAPY

Oxygen therapy must be carried out in all patients with a PaO₂ less than or equal to 60-70 mmHg or with saturation levels less than 95%. Oxygen can be administered by using different methods; some patients may require sedation with benzodiazepines and opiates. If the patient does not cooperate, it is preferable to use sedation rather than not to perform a lifesaving procedure such as oxygen therapy. The drugs most commonly used are butorphanol 0.1-0.2 mg/kg i.m, i.v or diazepam 0.1-0.2mg/kg i.v. associated with an opiate such as morphine or methadone 0.1-0.2 mg/kg i.v. In hypoxic cats that are particularly reactive and intractable, an oxygen cage is to be preferred; subsequent examinations or procedure should be performed only after stabilisation of the patient. Following is a list of the different procedures used for oxygen delivery.

Direct flow (flow-by: tube near the nostrils)
This technique is easy to perform, non-invasive and doable also while performing other procedures; it is considered the first choice solution during the examination and stabilisation of the patient. To execute this technique an oxygen therapy tubing has to be connected to an oxygen source than can deliver oxygen at high volumes (e.g. oxygen cylinder or oxygen circuit); the use of an  anaesthesia circuit  is not indicated as it may contain residual anaesthetic gasses that are irritating to the airways. In such cases, the administration of oxygen can get particularly difficult as the patient may refuse treatment because of the irritating and foul smelling nature of the gas. The volume of oxygen to be dispensed is dependent on the size of the patient. The administration of 2-5 L/min is sufficient to obtain a FiO₂ percentage of around 30–48%.^₃ High flows allow oxygen insufflation even during the expiratory phase, thus maintaining the alveoli open during all phases of ventilation. The flow must be directed in proximity of the nostrils (Fig. 3); a high flow directed against the oral cavity may produce gastric dilatation. The technique is very simple but requires the constant presence of an operator and the use of considerable quantities of oxygen. It is usually used in the initial stages and is subsequently replaced with more effective and less expensive techniques.

Intranasal and nasopharyngeal catheter
This is a technique that allows to obtain a FiO₂ percentage of about 40% without loss of oxygen and  which is indicated for long-term (hours or days) and short-term treatments; it is easy to perform and well tolerated by most patients. It may require sedation and only rarely anaesthesia induction. Manipulations or procedures on the patient are possible without having to interrupt the oxygen delivery. Transparent catheters made of polyvinyl chloride or polyurethane can be used. The catheters should be small: 4-8 French. Before application, the catheter must be pre-measured by placing the rounded distal end in proximity of the nasal canthus of the eye and the proximal end in correspondence with the alar cartilage of the nose. A marking with a permanent marker or rather with adhesive tape should be made on the proximal end; the tape will be later used to fasten the catheter. Before inserting the catheter it is recommended to instil 2-3 drops of 2%  lidocaine into the nostril and to then apply some lubricant gel on the distal end of the catheter. The catheter must be inserted ventrally and medially to the pre-measured length. It is then fastened to the skin in the vicinity of the nose-skin junction on the side of the alar cartilage with 1-2 interrupted sutures;  a mounted 3-0 non-resorbable suture must be used ( Fig. 4). The remaining part of the catheter is fastened to the skin with interrupted sutures on the side of the head or in correspondence with the frontal bones so that the tube does not enter into the visual field of the patient; finally, a last suture is made into the nuchal region. In emergency conditions, the catheter can be temporarily fastened even with a mechanical stapler for cutaneous sutures (35R). To place a nasopharyngeal catheter, the catheter is inserted as in the previously mentioned technique until the premeasured marking, which in this case goes from the tip of the nose to the mandibular branch. In both modalities the oxygen flow must be delivered at a speed of 50/150 ml/kg/min, achieving  a FiO₂ percentage of 30-70%  respectively. The intranasal administration of oxygen can also be done using transparent paediatric oxygen therapy catheters, known as paediatric nasal cannulas  (Fig. 5), which are provided with two short spouts to be inserted into the nasal cavity. When using this latter device for prolonged periods, the cannula should be anchored to the skin with a few sutures similarly to the oxygen tube indicated above. The oxygen must be humidified in order to avoid dehydration of the airways.

Transtracheal catheter
 The transtracheal catheter makes it possible to overcome the mechanical or functional obstructions (e.g. laryngeal paralysis) of the upper airways, and it may also be used in patients which cannot tolerate the nasal catheter or have a facial conformation (e.g. brachycephalic subjects) which makes the application of a nasal catheter difficult or impossible. It is less irritating than the nasal catheter, but it is more invasive, more difficult to position, and requires an analgesic treatment and an anaesthetic induction for its application. A flexible catheter is used, longer and with a larger diameter than the previous ones. This method makes it possible to obtain a FiO₂ percentageof 100% and a positive pressure insufflation during all phases of respiration. The point of insertion of the catheter should be chosen between the first and the fifth tracheal ring; the area of ​​skin must be prepared like a surgical field and a local anaesthesia of lidocaine 2% (1-2 ml ) is administered. The catheter can be inserted by using two different methods: the first involves the use of a large needle inserted between the tracheal rings and through which the catheter slides up to the premeasured point (chest entry); the second method uses curved haemostat forceps that must be inserted through the tracheal rings after a small skin incision is made with a scalpel blade. After inserting the forceps, the catheter slides through the breach thus made. The catheter must be secured to the skin with several interrupted sutures, the first in correspondence with the insertion, another one laterally to the neck and the last one dorsal to the neck. The catheter must be positioned a few centimetres cranially of the bifurcation of the sternum. The oxygen flow should be of 50-150 ml/kg/min. Flows of 50 ml/kg/min make it possible to obtain a FiO₂ percentage of 40-60%.^₅  Catheter displacements can cause subcutaneous emphysema, hence the insertion site must be constantly checked to ensure that the tube does not kink at the insertion site in the neck or that no local infections occur. 

Elizabethan collar with oxygen (Crowe collar)
The Elizabethan collar equipped with a source of oxygen may used temporarily in patients who cannot tolerate the intranasal application of the catheter (e.g. biting subjects), pending the application of another effective device that does not waste as much oxygen. After the application of the collar, ¾ of its anterior portion are closed with a film of transparent plastic, which hinders the diffusion of oxygen in the ambient air. Inside the collar, in its ventral part, the end of the tube which delivers the oxygen is fastened with some tape. The oxygen flow must be of 100-200 ml/kg/min in order to obtain a FiO₂  percentage of about 40%. To maintain the collar in the correct position (with the opening upward and the delivery tube downward ) a slight weight should be applied to the outer ventral side of the collar. When applied to small-size patients with a high respiratory rate, an accumulation of water vapour, carbon dioxide and an increase in body temperature may be present. 

Oxygen Cage
The oxygen cage, in addition to controlling FiO₂, allows to ensure that the temperature and humidity are  kept constant. The method has some disadvantages: it does not allow the contact with the patient and the opening of the cage causes the rapid fall of FiO₂ which must be then restored with high flows of oxygen. The oxygen cage is very useful for patients who do not tolerate intranasal catheters and especially in cats with acute respiratory distress (e.g. feline asthma). It is considered the first choice solution in emergencies until an intranasal catheter may be used and when needing to control the ambient temperature and humidity. To maintain FiO₂ at 40%, 5 to 15 L/min are needed, depending on the size of the cage.

TOXICITY OF OXYGEN THERAPY

The administration of oxygen with FiO₂ at 60% for longer than 48 hours or with a FiO₂ percentage at 100% for 24 hours or more can cause lung damage (lung toxicity from oxygen). The toxicity is due to the formation of cytotoxic oxygen free radicals that can produce severe pulmonary dysfunction. The toxicity is manifested by a progressive decrease in lung compliance that can be produced by an irreversible pulmonary fibrosis, associated with the development of interstitial or intra-alveolar haemorrhagic oedema. The mechanism underlying the toxic effects is not known; it is assumed that oxygen acts directly on lung tissue. The presumed biochemical pathogenesis recognizes the action of the oxygen free radicals as the cause of the damage produced in the lung tissue. The protective antioxidants which are normally present in the fluids lining the respiratory tract (mucin, proteins, uric acid, ascorbic acid, glutathione reductase and superoxide dismutase) are consumed by an excessive oxidative action. Other possible indirect factors include an increased sympathetic activity, a reduced surfactant activity, collapse and atelectasis of the pulmonary parenchyma. The greater the amount of FiO₂, the longer the duration of treatment and the higher the degree of individual sensitivity, the more serious is the toxicity. Clinically, oxygen toxicity is difficult to diagnose as the symptoms may be similar to those of acute respiratory distress syndrome (ARDS). Should the patient not show signs of improvement notwithstanding the oxygen therapy (PaO₂ ≤ 60 mmHg), positive pressure ventilation should be considered in order to avoid difficult to treat phenomena of toxicity correlated to oxygen therapy.

References

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