Hypercapnia is defined as an excess of carbon di oxide in the body.

The degree of hypercapnia which can be tolerated depends not only on the failure of homoeostasis but also availability of oxygen .

Classification of hypercapnia : MODERATE HYPERCAPNIA : PCO2 range

40 – 100 mmhg SEVERE HYPERCAPNIA : PCO2

greater than 100mmhg

The classification emphasizes that a PCO2 more than 100mmhg is unlikely to occur when a patient is breathing air , since dilution of oxygen in the alveolar gas by the raised carbon dioxide level causes severe hypoxia .

It has also been observed that 100mmhg represents the upper limit of hypoxia which can be compatible with life in patients with severe lung disease .

PARTIAL PRESSURE OF GASES IN ALVEOLI

Normal ventilation

Arterial pco2 =40mmhg

Hypoventilation

pco2=100mmhg

oxygen 95 mmhg 35mmhg

nitrogen 578mmhg 578mmhg

Carbon dioxide 40mmhg 100mmhg

Water vapor 47mmhg 47mmhg

total 760mmhg 760mmhg

Hypercapnia and central nervous system The effects of CO2 on CNS are complex ,the

total effect observed is a balance between at least three major actions. They are

It effects on cerebral blood flow and CSF pressure

Its influence on intracellular Ph causing secondary effect within the cell ,particularly those of the reticular activating system and hypothalamus

Its inert gas narcotic effect

Hypercapnia and cerebral blood flow CBF varies directly with Paco2 The effect is greatest within the range of physiologic

Paco2 variation. CBF changes 1 to 2 ml/100g/min for each 1mm Hg

change in Paco2 around its normal value. Changes in CBF caused by Paco2 are apparently

dependent on PH alteration in the extracellular fluid of the brain

Neuronal origin , NO and prostaglandin play the role of mediator in CO2 induced vasodilatation

A patient who has had a sustained period of hyper or hypoventilation deserves a special consideration. Acute normalization of Paco2 will result in significant CSF acidosis .

CARBON DIOXIDE NARCOSIS

Carbon dioxide was the first gas to be used in search for surgical anaesthesia by Henry Hill Hickman in 1842.

Slight elevation of Paco2 causes direct cortical depression and increase the threshold for seizure

Higher levels of CO2 stimulates subcortical hypothalamic centers which results in increased cortical excitability and seizures

Further elevation of CO2 causes an anaesthetic like state of cortical and subcortical depression.

Hypercapnic narcosis is associated with marked ventilatory and circulatory stimulation with increased muscle tone and cortical seizure activity.It were these characteristics which finally deterred anaesthetists from their attempts to use co2 as an anaesthetic agent.

The depressant effect of carbon dioxide are probably due to

Reduction of intracellular Ph

Inhibition of synaptic transmission in the brain and spinal cord

Reduced intracellular Ph is associated with disturbances of membrane electrolyte transport, interference glucose utilization and substrate delivery and inter cellular amino acid depletion.

Acute hypercapnia causes decrease in glycogen store and increase in glucose 6 phosphate and fructose 6 phosphate , but a marked decrease in delivery of pyruvate and lactate.

There is inhibition of glycolytic pathway and TCA cycle ,but an increase in succinate level.

Decrease delivery of pyruvate from normal glycolytic pathway → increase use of amino acid as an alternative source of pyruvate →decreased amino acid pool in the brain and increase in ammonia content due to oxidative deamination→ increased activity of asparate amino transferase →glutame depletion and increased asparate formation

The degree of brain intracellular Ph disturbance is dependent on the degree of intracellular buffering of the induced change of PaCo2.The regulation of brain Ph is time dependent and for a given sustained level of Ph ,intracellular Ph regulation reaches 90℅ of the theoretical possible value within three hours and thereafter changes are very little.

Three mechanism that contribute to the buffering of intacellular Ph :-

Physiochemical buffering Consumption of organic acid Trans membrane exchange of H and HCO3 ion

Woodbury et al (1958) posttulaed three levels of brain excitability in response to hypercapnia .

Stage one : progressive depression upto Paco2 150mmhg

Stage two : excitation and convulsion Stage three : progressive depression of

cerebralar electrical activity

Autonomic effect of Hypercapnia Hypercarbia induces generalized stress response in

the body by secreting adrenaline and nor adrenaline During anaesthesia hypercarbia induced stress can

be modified by the drug used. Price et al found higher level of catecholamine under

cyclopropane anaesthesia than those under halothane

there is enhancement of many responses to infused catecholamine during moderate hypercapnia.

contd………

But most aouthor agreed that inhalation of more than 15℅ co2 can depress the chronotropic, ionotropic and pressor response to infused adrenaline

Inhibitory reflexes mediated through parasympathetic pathway are enhanced by moderate hypercarbia.

In condition where over activity of the sympathetic nervous system occurs (ex tetanus) , circulatory responses to moderate hypercarbia are greatly exaggerated

CIRCULATORY RESPONSE TO HYPERCAPNIA Hypercapnia has got characteristic dual effect

on circulation :-. Depressant effect of the gas on target organ Central excitation of sympathetic nervous systemAnd, over all picture is influenced by age, type

of anesthesia, duration and severity of hypercapnia , mode of ventilation and so on

Increased Paco2 and associated acidosis decreases myocardial contractility, heart rate and the contractility of isolated papillary muscle but the effect is short lived and there is progressive recovery of function as the intracellular Ph changes are buffered.

Hypercarbia has a depressant effect on peripheral vascular resistance , mostly on

precapillary resistance section

HAEMODYNEMIC EFFECT ( CONSCIOUS STATE) An elevation of Paco2 (39 -50 mmhg) in

conscious patient during controlled or spontaneous ventilation causes marked increases in heart rate , myocardial contractility,consequent increase in cardiac output while SVR is reduced .

HAEMODYNEMIC EFFECTS (UNCONSCIOUS)Volatile anaesthetic modify the haemodynamic

effect of elevated Paco2 .The direct effect of all anaesthetic is to impair myocardial contractility which is common with high Paco2.

Cyclopropane, fluroxene, di ethyl ether, isoflurane and enflurane enhances the sympathetic effect of raised Pco2.Where as nitrous oxide and halothane do not.

Contd…

The effect of hypercapnia on ventricular performance is dependent on hydraulic impendence to left ventricle .( SVR and the ratio of mean arterial pressure to cardiac output.) Hypercapnia almost associated with marked reduction SVR and the non pulsatile term of aortic input impedance, thus the depressant effect of anaesthesia and CO2 on the ventricular muscle are to some extent offset

Decrease in SVR is most marked in Enflurane , though seen with most anaesthetic .

CARDIOVASCULAR RESPONSES TO HYPERCAPNIA DURING VARIOUS TYPES OF ANAESTHESIA

HEART

RATE

CONTRACTILITY

CARDIAC

OUTPUT

SYSTEMIC VASCULAR

RESISTANCE

CONSCIOUS ++ ++ +++ -NITROUS

OXIDE0 + ++ --

CYCLOPROPANE +++ ? +++ ---DIETHYL ETHER ++ ++ +++ --HALOTHANE 0 + + -ENFLURANE + + ++ ----ISOFLURANE ++ +++ +++ -

HYPERCAPNIA, ANAESTHSIA AND β ADRENO RECEPTOR BLOKADE The main sympathetic effect of hypercania

are mediated through adrenergic β receptors In the presence of β receptor blockade,

effects of hypercapnia on sympathetic nervous activity are inhibited , leaving the direct myocardial depressant effects of carbon dioxide to produce additive effects with the anaesthetic agents

Propanolol has a selectivity for peripheral vascular β receptor rather than heart and since it doesn't block ά receptors ,circulating catecholamine exert an unopposed vasoconstrictor effect on systemic blood vessels .Thus combination of hypercapnia ,anaesthesia and β receptor blockade may increase rather than decrease SVR.

HYPERCAPNIA AND CARDIAC ARRYTHMIA It is widely accepted that hypercapnia is associated

with alteration in cardiac rhythm and conduction in presence of certain anaesthetic agent .

In conscious patient cardiac arrhythmia are unusual upto 80mmhg of Paco2.

The threshold of paco2 at which arrhythmia may occur may be modified by various anaesthetic agent.(cyclopropane, halothane etc )

CONTD……..

Contd…

Halothane ,enflurane and isoflurane have been shown to prolong QT interval in human ,there by increasing the risk of torsades the point ventricular tachycardia

Torsades the point is notorious for decompeseting into ventricular fibrillation

HYPERCAPNIA AND VENTILATION PACO2 = VCO2 / VA (PB – 6.27) (kpa)So, PACO2 is determined by alveolar ventilation (VA )

and CO2 production (VCO2 But if the inspired gas contains carbon dioxide than

the equation will be FACO2 = FICO2 + VCO2 / VA When FICO2 approaches FACO2 , constancy of

latter is no longer maintained despite an increase in ventilation .The body tends to compromise by tolerating a slight increase in FACO2 rather than increasing alveolar ventilation to the point at which FACO2 is returned to normal.

The response to increased metabolic CO2 production is more efficient since ventilation is usually sufficient to maintain a normal FACO2 under condition of raised VCO2 .

CARBON DIOXIDE / VENTILATION RESPONSE CURVE The relationship between the expired minute

volume and the alveolar or arterial PCO2 defines the carbon dioxide / ventilation response curve .

The slope of curve reflects the over-all sensitivity of the reflex ventilatory response to increased FACO2 .

Its spatial position indicates the threshold of response to a given FACO2

The normal ventilatory response to hypercapnia arises by two mechanism :-

peripheral chemoreceptor response to increasing PCO2 in arterial blood

the response of neurons in the floor of fourth ventricle of the brain to a reduction of CSF Ph.

The relationship between hypercarbia and minute ventilation can also be expressed by following manner

Vm =S(PETco2 – B) Where Vm is minute ventilation S is ventilatory sensitivity to CO2 B is apneic threshold The value of S shows large intra and inter subject

variability .Apart from genetic variability the value S depends on sex, female and male sex hormone, age , physical training ,circadian rhythm ,behavioral state ,underlying disease, ambient oxygen tension and acid- base status

In awake human, the conscious drive to breath and other stabilizing influence on respiration maintain breathing, when CO2 tension is below resting value. This results in a flattening of the CO2 response curve at lower CO2 level .This is referred as a dogleg or hockey stick .

When consciousness is lost , as with sleep or anaesthesia apnea occur when there is hypocapnia ; dogleg disappears and a true apneic threshold point is found

An increase in arterial CO2 tension increases ventilation by stimulating both peripheral and central receptors .

Dynamic end- tidal forcing technique was developed to quantify the separate contribution of central and peripheral receptors .This technique shows that peripheral receptors takes 6 secs to react to hypercarbia where as central receptors takes 12 secs to do the same.

In awake patient ,the contribution of peripheral and central receptors to CO2 stimulated ventilation is 30% and 70% respectively .

PULMONARY GAS EXCHANGE AND OXYGEN TRANSPORT Hyperdynemic circulation during hypercapnia in an

anaesthetized person, transport of oxygen between lung and tissue is enhanced by increased cardiac out put and reflected by lower than normal ateriovenous oxygen content differrence.

Alveolar arterial PO2 difference is reduced due to higher oxygen content in mixed venous blood and less venous admixture

But this slight increase in arterial PO2 is offset by impaired uptake of oxygen by hemoglobin ( bohr effect on oxygen dissociation curve )

The gross displacement of the curve to the right accounts for desaturation of arterial blood despite normal oxygen tension .

HYPERCAPNIA AND REGIONAL BLOOD FLOW PULMONARY CIRCULATION Hypercapnia causes increase in pulmonary

arterial pressure in most circumstances that is associated with increase pulmonary blood flow. Although Co2 has some direct vasoconstrictor effect , vasoconstriction is mainly due to effect of acid on pre and post capillary vessels .

CORONARY CIRCULATION Hypercapnia increases coronary blood flow

which is disproportionate to the increase in the left ventricular work and myocardial O2 requirement .This effect is associated with marked increase in coronary sinus PO2 and consequent decrease in the arteriovenous O2 content difference across coronary circulation

HEPATIC AND SPLANCHNIC CIRCULATION The influence of hypercapnia on pressure flow

relationship in the splanchnic and hepatic circulation varies considerably according to anaesthetic drug used

During thiopentone and nitrous oxide anaesthesia sympathetic adrenergic response to hypercarbia are not unduly suppressed , so hypercapnia is associated with splanchnic vasoconstriction and reduced hepatic blood flow

During halothane anaesthesia the balance is such that the vasodilator effect of carbon dioxide promotes splanchnic vasodilatation and marked increase in hepatic blood flow .

LIMB BLOOD FLOW

The two major vascular circuits in the limb are those to skin and skeletal muscle .

In both circuits the response to hypercapnia is balance between the direct vasodilator effect of CO2 and vasoconstrictor effect secondary to sympathetic adrenergic activity.

During anaesthesia , the response is predominantly vasodilator in skin and vasoconstrictor in muscle .

HYPERCAPNIA AND BODY TEMPARATURE Schafer et al observed that during the first 6-12

hours of sustained hypercarbia in response to breathing 15% carbon dioxide , body temperature falls by about 3.c , but recover to the original value in a period of three days .

The reduction of body temperature is due to Direct inhibition of cellular metabolism . Increased heat loss due to vasodilator effect of

CO2 on skin blood vessels A transient decrease , followed by a sustained

increase in the nor adrenaline content of cells in the hypothalamic region involved in thermoregulation

OBSTRETICS AND NEONATAL IMPLICATION OF HYPERCAPNIA The generalized circulatory effects of

hypercapnia are reflected in changes in both maternal and fetal circulation. With consequent effect on fetal oxygenation

.Ivanko , Elam and Huffman observed that moderate hypercapnia in the human mother during caesarian section is associated with elevated umbilical PO2 .

ACID BASE EQULIBRIUM DURING HYPERCAPNIA With a normal caloric intake of a meat-based diet the

average person will generate approximately 20,000 mEq of acid/day in the form of CO2 as the end-product of carbohydrate and fat metabolism.

So hypercarbia ;exogenous or endgenous represents the greatest stress which is imposed on the homeostatic mechanism for maintenance of blood and tissue fluid neutrality .

An increased in the alveolar Pco2 from whatever the cause results in progressive build up of carbon dioxide stores ;reflected in the increased Pco2 of both arterial and mixed venous blood

Inside the red cells co2 when combines with water produces H + and HCO3- ions in the presence of carbonic anhydraes

CO2 + H2O ↔H2CO3 ↔ H + + HCO 3-

If co2 increases , the equilibrium is displaced to the right

The kidney compensates for acidosis by excreting H+ ions and retaining bicarbonates .

When there is acute rise in co2 that is not uncommon intra operatively, kidney doesn’t get time for compensation. But in chronic hypercarbia , due to compensatory mechanism arterial Ph is much higher for the corresponding acute change of Pco2

PERMISSIVE HYPERCAPNIA

Satisfactory oxygenation with low TV & PIP (30-35cm H2O) can be achieved at the cost of increase PaCO2

Allow slow increase in PaCO2 Be cautious in patients with IHD/LVF Avoid in pt with increase ICT

PERMISSIVE HYPERCAPNIA

Beneficial effects of increased PaCO2

-Increased cardiac output due to increased

sympathetic activity

-Increased splanchnic & renal blood flow

-Monitor pH, do not allow to fall <7.2/ 7.3