Hypoxia: Deadly killer in Anesthesia

History of oxygen:

    Colorless, odorless diatomic gas discovered by Priestley in 1771 which is manufactured by fractional distillation of air. 21% volume of Atmospheric air is occupied by oxygen. Other gases are:

Atmospheric Air

¨      Nitrogen                               78.00%

¨      Oxygen                                21.00%

¨      Co2                                     0.03%

¨      Others                                0.97%

   Despite of some dark sites oxygen is essential for cellular respiration. This oxygen is transported from air to mitochondria of a cell via series of steps by changing its partial pressure. This gradual change of partial pressure of oxygen up to mitochondria has been termed as oxygen cascade.

Oxygen Cascade.

Partial pressure at different levels                 mm of Hg

Dry atmospheric gas ( PiO2)                                 160

Humidified alveolar gas (PAO2)                            106

Po2 in Venous end of Pul. Capillary                        100

Systemic Artery (PaO2)                                         95

Po2 in ISS                                                             40

Po2 within the cell                                                    23

   Reduction in the partial pressure of oxygen in the cascade may lead to marked reduction of partial pressure in mitochondria and if pressure falls below a critical level Anaerobic metabolism occurs in the body. This critical point of mitochondrial PO2 has been termed as Pasteur Point. It is about 0.15-0.3 kPa

Oxygen Transport

Oxygen is transported in the blood by two ways:

1. In dissolved form which constitutes 3% of total oxygen volume and
2. In combination with Hb which constitutes about 97% of total volume of oxygen

Dissolved in plasma (3%)

0.003 ml/mm of Hg/dl of blood

Dissolved state of oxygen in the blood is determined by Henry’s law. About 0.3 ml of oxygen is dissolved in100 ml of blood at 95 mm of Hg.

It is responsible for Po2 in the blood.

In combination with Hb (97%)

1. About 1.34 ml of   O2 can combine with 1 gm of Hb at 100 mm of Hg at 37°c

• arterial blood contains about 19.8 ml O2/dl of blood
• venous blood contains about 15.2 ml O2/dl of blood

So under normal condition tissue removes average 5 ml O2 per dl of blood. Therefore body consumes average 250 ml O2 per min.

Our body operates in a very low oxygen environment and it will take about 3-4 minutes to burn total O2 volume of blood for Aerobic metabolism. So optimum functioning of oxygen cascade is essential for optimum tissue oxygenation. Otherwise body will experience reduced oxygenation at tissue level. This has been termed as hypoxia.

Hypoxia

Oxygen deficiency at tissue level

Or

Reduced oxygen for tissue respiration

Hypoxia has been classified in many ways. But there are basic four types of hypoxia.

Types:

• Hypoxic
• Anaemic
• Histotoxic
• Stagnant

Hypoxic Hypoxia

Reduced oxygen tension in the blood.

Hypoxic hypoxia is also called hypoxaemia when Po2 <80 mm of Hg.

Causes:

           Alveolar  hypoventilation

                         -drug overdose

                         -COPD exacerbation

          pulmonary diffusion defect

                         -pulmonary fibrosis

                         -Emphysema

                         -pulmonary oedema

           Pulmonary V/Q mismatch

                         -Asthma

                         -pulmonary embolism

           R-L shunt

                         - Atelectasis

                         - Cyanotic congenital heart disease

            ? FiO2 or PBaro 

Anaemic

In anaemic hypoxia PaO2 is normal but there is insufficient amount of functional hemoglobin to carry O2

 Occurs in Anaemia and CO poisoning

In anemic hypoxia we should correct anaemia first before going oxygen therapy because-

• 50% reduction of Hb causes 50% reduction in CaO2 but
• 50% reduction of PaO2 causes 18% reduction in CaO2

Stagnant

Also called Ischaemic  hypoxia

Here Hb conc. and Po2 are normal but there is slower blood flow to the tissue

Occurs in –CCF

                 -Atherosclerosis

Histotoxic

In Histotoxic hypoxia 

 -PaO2 is normal

                                        -Hb conc. is normal

                         -supply of O2 to the tissue is normal

 -But tissue can’t utilize supplied O2

Occurs in –

 Cyanide poisoning

 Chronic CO poisoning

Sign and Symptoms

Successful treatment of tissue hypoxia requires early recognition. This can be difficult because the clinical features are often non-specific and include-

CNS

Nausea

Headache

Drowsiness

Confusion

Convulsion

Unconsciousness

Hb Saturation

           85%------- Mental impairment

                       75%-------- Severe Mental impairment

                                 65%-------- Unconsciousness

Respiratory

                   Hyperventilation

                   Pulmonary HTN

Kidney

                   Function impaired

CVS

                   Tachycardia

                    Bradycardia                                       

                    Arrythmia

                    Asystole

We should be aware of cyanosis. Cyanosis is something when it is present but if it is absent it doesn’t mean anything about oxygenation status. It may be absent in-

¨      Anaemic hypoxia(5gm% deoxygenated blood required)

¨      CO poisoning

¨      Histotoxic hypoxia

Cell injury and Hypoxia

¨                  The first point of attack of hypoxia is the cell’s aerobic respiration

¨                  If Partial pressure of oxygen in the tissue reaches to a level below    Pasteur Point it starts Anaerobic respiration which causes marked depletion of ATP

¨                  Reduced ATP production causes failure of energy dependent pumps which causes cellular swelling, reduction of pH and structural destruction of protein.

¨                  Further reduction of oxygen tension causes development of large , amorphous, flocculent densities in mitochondrial matrix

¨                  Injury of Lysosomal membrane and leakage of its enzyme

Point of no Return

If hypoxia persists for a certain period different tissues of the body may undergo irreversible damage.

Brain               3-5 min

Heart               30-40min

Kidney             45 min

Liver                1-2 hours

Measurement

• Hb saturation with O2

Oxymetry(SaO2, SpO2)

• O2 Content

Vas Slyke apparatus

• Partial Pressure of Oxygen

Oxygen electrode

• SaO2 and PaO2 are the principal clinical indicators for initiating, monitoring, and adjusting oxygen treatment.
• However SaO2 and PaO2   can be normal in hypoxia caused by low cardiac output, anaemia and Histotoxic hypoxia. In these circumstances PvO2 is better index of tissue oxygenation.
• But PaO2 and PvO2   may be normal in severe hypoxia in single organ. In this case specialized techniques including Tonometry and Oxygen probes are helpful.

Management

Appropriate management of hypoxia depends on treating the underlying cause while providing supplemental oxygen as necessary.

  Oxygen therapy

There are some rules of Oxygen therapy:

1. Give Oxygen to the patient as much as you can at first and then reduce it, guided by blood gas measurement
2. oxygen treatment will work only if the patient have a patent airway
3. Definitive treatment of hypoxia depends on the underlying cause; giving oxygen is a holding measure.

    Clinical goals of oxygen therapy:

1. Treatment of hypoxaemia
2. ? work of breathing
3. Decrease myocardial work load

When to start?

“American College of Chest Physicians and National Heart Lung and Blood Institute” recommendations for instituting oxygen therapy:

• Cardiac and respiratory arrest
• Hypoxaemia (PaO2<60 mm Hg, SaO2<90%)
• Hypotension (systolic blood pressure <100 mm Hg)
• Low cardiac output and metabolic acidosis (bicarbonate<18 mmol/l)
• Respiratory distress (respiratory rate >24/min)

Oxygen therapy in Anaesthesia

Hypoxia is not uncommon in patient under Anaesthesia and in post operative ward. Oxygen therapy should be given:

Before induction

                   To enrich FRC

Under anaesthesia

To correct hypoxaemia resulting from:

• Hypoventilation due to Anaesthetic drugs and Opioids
• V/Q mismatch
• ?FRC
• closing volume encroaches VT

During recovery

To prevent

Diffusion Hypoxia

Post Operative

Routine 10 min following GA:

• IHD
• ? CO
• Anaemia
• Obesity
• Hypothermia
• shivering
• Pul Oedema
• Airway obstruction

In post operative ward patient may experience severe hypoxia due Hypoventilation as a result of severe pain. So appropriate management of pain is a part of successful treatment of hypoxia along with oxygen therapy.

Devices

High-Flow OR Fixed-Performance devices: HAFOE, Anaesthetic Breathing System, Ventilator

          The delivered FiO2 is not affected by variations in ventilatory level or breathing pattern. These devices are suitable for patients who require:

•  A constant FiO2
•  Large inspiratory flows of gas (>40L/min)

Variable performance devices: Nasal canula. Face mask

          Delivered FiO2 is affected by variations in ventilatory level or breathing pattern.

Low flow systems are adequate for patients with:

• Minute ventilation less than 8-10L/min
• Breathing frequencies less than 20 breaths/min
• Tidal volume less than 0.8 L
• Normal inspiratory flow(10-30 L/min)

Dark sides of Oxygen

1. Joseph Priestly

Fire

   Oxygen supports combustion of fuels. An increase in the concentration of oxygen from 21% up to 100% causes a progressive increase in the rate of combustion with the production of either conflagrations or explosions with appropriate fuels.

Cardiovascular depression

   An increase in PO2 leads to direct vasoconstriction, which occurs in peripheral vasculature and also in the cerebral, coronary, hepatic and renal circulations. This effect is not manifest at PaO2 of less than 30 kPa and assumes clinical importance only at hyperbaric pressures of oxygen. Hyperbaric pressures of oxygen also cause direct myocardial depression. In patients with severe cardiovascular disease, elevation of PaO2 from the normal physiological range to 80 kPa may produce clinically evident cardiovascular depression.

Absorption atelectasis

   Because oxygen is highly soluble in blood, the use of 100% oxygen as the inspired gas may lead to absorption atelectasis in lung units distal to the site of airway closure. Absorption collapse may occur in as short a time as 6 min with 100% oxygen, and 60 min with 85% oxygen. Thus, even small concentrations of nitrogen exert an important splinting effect and this accounts for current avoidance of 100% oxygen in estimation of pulmonary shunt ratio (Qs/Q.t) m patients with lung pathology, in whom a greater degree of airway closure would result in greater areas of alveolar atelectasis. Absorption atelectasis has been demonstrated in volunteers breathing 100% oxygen at FRC; atelectasis is evident on chest radiography for a period of at least 24 h after exposure.

Co2 narcosis

   In patients with chronic bronchitis and chronic CO2 retention, there may be loss of sensitivity of the central chemoreceptors and some dependence of ventilation on drive from the peripheral chemoreceptors that respond to oxygen. Administration of a high .FiO2 to such a patient may cause loss of peripheral chemoreceptor drive with the subsequent development of ventilatory failure.

Pulmonary oxygen toxicity

   Chronic inhalation of a high inspired concentration of oxygen may result in the condition termed pulmonary oxygen toxicity (Lorrain-Smith effect), which is manifest by hyaline membranes, thickening of the interlobular and alveolar septa by oedema and fibroplastic proliferation. The clinical and radiological appearance of these changes is almost identical to that of the acute respiratory distress syndrome. The biochemical mechanisms underlying pulmonary oxygen toxicity probably include:

• Oxidation of SH groups on essential enzymes such as coenzyme A

• Peroxidation of lipids; the resulting lipid peroxides inhibit the function of the cell

• Inhibition of the pathway of reversed electron transport, possibly

by inhibition of iron and SH-containing flavoproteins.

   These changes lead to loss of synthesis of pulmonary surfactant, encouraging the development of absorption collapse and alveolar oedema. The onset of oxygen-induced lung pathology occurs after approximately 30 h exposure to a PO2 of 100 kPa.

Central nervous system oxygen toxicity

Convulsions(Paul Bert effect), similar to those of grand mal epilepsy, occur during exposure to hyperbaric pressures of oxygen.

Retrolental fibroplasias
   Retrolental fibroplasia (RLF) is the result of oxygen-induced retinal vasoconstriction, with obliteration of the most immature retinal vessels and subsequent new vessel formation at the site of damage in the form of a proliferative retinopathy. Leakage of intravascular fluid leads to vitreoretinal adhesions and even retinal detachment. Retrolental fibroplasia occurs in infants exposed to hyperoxia in the paediatric intensive care unit and is related not to the FiO2 per se, but to an elevated retinal artery PaO2. It is not known what the threshold of PaO2 is for the development of retinal damage, but an umbilical arterial PaO2 8-12 kPa (60-90 mmHg) is associated with a very low incidence of RLF and no signs of systemic hypoxia. It should be stressed, however, that there are many factors involved in the development of RLF in addition to arterialhyperoxia.

Depressed haemopoiesis

Long-term exposure to elevated FiO2 leads to depression of haemopoiesis and anaemia.

Oxygen  induced cell injury

   The overzealous and unregulated use of supplemental oxygen must be tempered by the potential for oxygen to act as a powerful and even lethal toxin. In fact, contrary to the notion that oxygen protects cells from injury, the accumulated evidence suggests that oxygen (via the production of toxic metabolites) is responsible for much of the cell injury in critically ill patients. The following is a brief description of the dark (toxic) side of oxygen.

The intermediates in oxygen metabolism:

Superoxide radical

Hydrogen peroxide

Hydroxyl Radical.

Overzealous and unregulated use of oxygen must be tempered for the potential of it’s to act as a potential or even lethal toxin.

References:
   1. http://www.free-medical-books.webs.com
   2. The ICU book
   3. clinical Anesthesia morgan

Article By: Dr. Md. Rajib Pervez