Physiological Changes In Pregnancy and its

Anaesthetic implications

Dr. Swadheen kumar Rout 1st year P.G Dept. of Anaesthesiology M.K.C.G College & hospital

INDIA -204 / 1,00,000 live births.USA - 7 / 1,00,000 live births.

Although no studies in india, studies in usa have shown that, 4-5% of total deaths are due to over zealous anaesthetic practices & its complications.

So one must be familiar not only with the effect of various drugs and techniques on the pregnant women and foetus but also the physiological changes in pregnancy which alter response to anaesthesia.

Maternal Mortality Rate (MMR)

Pregnancy produces profound physiological changes(adaptive to stress) that become more significant as pregnancy progresses.

This changes can be due to: 1) Hormonal alteration. 2) Mechanical effect of gravid uterus. 3) Increased oxygen & metabolic requirement. 4) Haemodynamical alteration.

In addition unique challenges - two patients are cared for simultaneously , Failure to take care can be disastrous for one or both of them.

Physiological Changes In Pregnancy

Parameter Change

Blood volume + 30%

Plasma volume + 45%

Cardiac output + 30-50%

Stroke volume + 20-50%

Heart rate + 15-25%

Peripheral resistance - 15-20%

CVP, PAWP Unchanged

From Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. NewYork, Churchill Livingstone, 2000, p 34.

Cardiovascular changes

Fluid retention is the most fundamental systemic change of normal pregnancy.

The total plasma volume is increased during pregnancy 45%. The most marked expansion occurs in extra cellular volume (ECV) with some increase in intra cellular water.

The factors contributing – Increase sodium retention.(RAAS) Decrease in thirst threshold. Decrease in plasma oncotic pressure(↓ albumin)

Volume homeostasis

At term, maternal blood volume has increased by 1000—1500 mL in most women, allowing them to easily tolerate the blood loss associated with delivery.

Normal delivery = 400-500ml blood loss Cesarean section = 800-1000ml blood loss Blood volume does not return to normal

until 1—2 weeks after delivery

Volume homeostasis

Cardiac output(40%) increases to meet accelerated maternal and fetal metabolic demands. This increase is mostly due to an increase in stroke volume (30%) as heart rate increases only slightly (about 15%).

Heart rate elevation occurs in response to increased

oxygen demand. CO ↑ 40% by 12 weeks

50% for rest of pregnancy

60%-100% during labor & after delivery

CO highest right after delivery (release of aorto-caval compression) due to uterine contraction.

Cardiac Output Effects

Peripheral vascular resistance (VR) decreases due to the vaso-dilatory effects of progesterone and the proliferation of low resistance vascular beds in the inter-villous spaces of the placenta.

Because of the decrease in peripheral vascular resistance(inspite of increased CO), arterial blood pressure does not significantly change or may show a slight fall in a uncomplicated pregnancy.

Diastolic(20%) > Systolic(8%)The response to adrenergic agents and

vasoconstrictors is thus blunted.

Cardiovascular effects

Despite the increase in blood volume, there is no change in the central venous pressure(CVP) during pregnancy. This is likely due to dilated systemic and pulmonary circulations.

Cardiac chambers enlarge and myocardial hypertrophy is often noted on echocardiography.(eccentric due to activation of RAAS).

Also show variable ECG ,ECHO,CXR Changes.

Other changes

Effect of Pregnancy on Cardiovascular Investigations

Investigation Findings

Chest radiography Apparent cardiomegaly Enlarged left atrium (lateral views) Increased vascular markings Straightening of left-sided heart border Postpartum pleural effusion

ECG Right-axis deviation Right bundle branch block ST-segment depression on left precordial leads Q waves in lead III T-wave inversion in leads III, V2, and V3 Rotation of 15 degrees(QRS axis)

ECHO Trivial tricuspid regurgitation Pulmonary regurgitation (up to 94% at term) Increased left atrial size by 12%-14% Increased left ventricle end-diastolic dimensions by

6%-10% Inconsistent increase in left ventricle thickness Mitral regurgitation (28% at term) Pleural effusion (40% postpartum)

From Gei AF, Hankins GDV: Cardiac disease and pregnancy.

CVS:- Its Anaesthetic Implications

Occurs in 20% of women at term.

Aorto-caval compression

Compression of IVCCompression of lower aorta

↓ COP by 24% at term.↓ blood flow to kidneys, utero-placental circulation & lower extremeties Supine Hypotension syndrome

(hypotension associated with pallor, sweating, or nausea and vomiting)Decreases in cardiac output can occur in the supine position after the 28th week of pregnancy.

Fetal hypoxia

Compensatory mechanisms in

unanaesthetised Women

Venous Collaterals ↑ SVR & HR

ParavertebralVenous plexus

Abdominalwall Reduced during general

or regional anesthesia.

Severe Hypotension

Profound Fetal Hypoxia

Women with a 28-week or longer gestation should not be placed supine without left uterine displacement.

Can be done by

Left lateral decubitus Tilting the table

Left side down

Rigid wedge (>15 degree) under The right hip

Fluid preloading before neuro-axial anesthesiaIt does not completely avoid maternal hypotension but

It ↑ maternal COP → preserve utero-placentalblood flow.

Physical examination of the term pregnant woman may also be abnormal with auscultation commonly revealing a wide, loud, split first heart sound, an S3 sound, and a soft systolic ejection murmur.

Hence essential to differentiate abnormal cardiovascular changes from normal physiological changes of pregnancy.

• Criteria to diagnose cardiac disease during pregnancy:

1) Presence of diastolic murmurs.

2) Systolic murmurs of severe intensity (grade 3).

3) Unequivocal enlargement of heart (X-ray).

4) Presence of severe arrythmias, atrial fibrillation or flutter

Changes in the respiratory system during pregnancy involve the upper airways, minute ventilation, lung volumes, and oxygen consumption.

Major physiological changes occur in the respiratory system during pregnancy due to a combination of both hormonal and mechanical factors.

Dyspnoea is a common complaint in pregnancy affecting over half of women at some stage.

Respiratory changes

Respiratory Parameter ChangeOxygen consumption + 20 to 50%Minute ventilation + 50%Tidal volume + 40 % Respiratory rate Unchanged/ Slight increasePaO2 + 10%

PaCO2 - 15%

HCO3 - 15%

FRC (functional residual capacity) - 20%

From Birnbach DJ, Gatt SP, Datta S (eds): Textbook of Obstetric Anesthesia. NewYork, Churchill Livingstone, 2000, p 35.

Average maximum physiological changes associated with Pregnancy

Due to increased metabolic demands, Oxygen consumption (+ 20 - 50%) and minute ventilation(+40 - 50%) progressively increase during pregnancy. (Increased progesterone sensitizes the central respiratory center to carbon dioxide – directly stimulating ventilation)

The pregnant woman thus takes larger Tidal volumes(40-50%) to eliminate carbon dioxide.

Paco2 decreases to(28—32 mm Hg); significant respiratory alkalosis is prevented by a compensatory ↓ in pasma HCO3 concentration.

Respiratory changes

Hyperventilation may also increase Pa02.

Elevated levels of 2,3-diphosphoglycerate offset the effect of hyperventilation (↓PaCO2) on hemoglobin affinity for oxygen.

The combination of increased 2,3-DPG with increase in cardiac output enhances oxygen delivery to tissues.

Respiratory changes

The maternal respiratory pattern changes as the uterus enlarges

Diaphragm rises up(4cm) compensatory increases in

Antero-posterior diameters

Diaphragm motion not restricted Chest wall limitation

Thoracic breathing favoured over Abdominal

Respiratory changes

20% decrease in FUNCTIONAL RESIDUAL CAPACITY(FRC).

* No change in CLOSING CAPACICITY (CC) & VITAL CAPACITY

Pregnant woman has a smaller “air tank”.Non-pregnant woman

Respiratory: Importance for Anaesthesia

↓ FRC/CC + ↑O2 Consumption=

Rapid O2 de-saturation during periods of apnea (diminished capacity to tolerate apnea).

Supine Position & Regional Block further diminishes FRC

Pre-oxygenation prior to induction of general anesthesia should be given to avoid hypoxemia in pregnant patients.

Rapid devlopment of hypoxemia

Respiratory: Importance for Anaesthesia

Rapid gaseous induction

The decrease in FRC coupled with the increase in minute ventilation accelerates the uptake of all inhalational anesthetics.

↓FRC ® less dilution

↑MV ® rapid deep depth

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Hormonal Changes Capillary engorgement of respiratory tract mucosa

1) ↑ Incidence of difficult intubation.2) Trauma and bleeding during endotracheal intubation.

Respiratory: Importance for Anaesthesia

☼ Repeated attempts at laryngoscopy minimized

☼ Use a small ETT (6 – 7 mm) during GA

1) Progressive decrease in MAC .

40% at term (Returns to normal by 3rd day postpartum).

CNS changes & its Anaesthetic importance.

Progesterone increases20 times normal

level at term

β- endorphin surge during labor & delivery

LA requirements for subarachnoid or epidural anaesthesia are reduced in pregnancy (30%)

a) ↑ diffusion of LA to the receptor site.

b) ↑ sensitivity of nerve fibres to LA (Lower CONCN. needed).

c) engorged epidural venous plexus.

d) ? raised CSF progesterone levels.

Spinal ligaments including ligament flavum ® SOFT hence loss of resistance technique used for regional block may be masked

CNS : its anaesthetic importance

IVC obstruction by enlarging

uterus

CNS : its anaesthetic importance

Engorged Epidural Venous Plexus

1) ↓CSF Volume

2) ↓Volume ofEpidural Space

3) ↑Epidural space Pressure

1,2: This enhances the cephalad spread of LA during regional blocks.

3 : Predisposes to higher incidence of dural puncture & intravascular injection

GIT Changes & its Anaesthetic importance

The parturient should be considered a full stomach patient

during most of gestation

☼ Upward & ant. displacement of the stomach by the uterus → Incompetence of gastro-esophageal sphincter → Gastro-esophageal reflux & aspiration.

☼ ↑ Progesterone → ↓ tone of gastro-esophageal sphincter.

☼ Placental Gastrin → Hyper-secretion of gastric acid.

☼ Gastric emptying → Delayed with labor.

Narcotics and anti-cholinergic reduce lower esophageal sphincter pressure (used with

precaution)

For GA:Pharmacological prophylaxis against aspiration.

Supine position with lateral tiltNo positive pressure ventilation before intubation

Rapid sequence induction. Sellick’s maneuver

Renal vasodilatation increases renal blood flow early during pregnancy.

↑ Cardiac output(CO) ↑ GFR & ↑ RPF(renal plasma flow) by 50%.

↑ Renin & Aldosterone level promotes Na+

retention leading to volume overload.

↓ Renal tubular threshold for glucose & amino acids → mild glycosuria & proteinuria (< 300mg/d).

RENAL changes & its anaesthetic importance

↑ GFR

Anaesthetic importance:↑ clearance of urea, uric acid and creatinine

↓ plasma concentrations of sr. Creatinine & BUN

BUN and Creatinine levels that would be considered marginally elevated in pre-pregnant patients are usually indicative of severe renal impairment in pregnancy.

Hepatic function and blood flow are unchanged.A mild ↓ in serum albumin is due to an expanded

plasma volume. Thus, the free fraction of albumin-bound medications is increased.

A 25—30% decrease in serum pseudocholinesterase activity is also present at term,but it rarely produces significant prolongation of SCh action.

Increased cholesterol gall stone formation(progesterone).

Hepatic effeccts

Hematological changes ↑ Blood Volume ( up to 90ml/Kg)

↑ by 1000 – 1500 ml at term.

↑ Plasma Volume(45%) > ↑ RBC mass(30%)

Dilutional anemia & ↓ blood viscosity

Facilitates maternal & fetal exchange of respiratory gases,

nutrients & metabolites

↓ Impact of maternal blood loss at delivery

• Pregnancy leads to a hypercoagulable state, due to,

a) factors VII, VIII, X, XII ,IX ( only factor XI ¯ )

b) fibrinogen and FDP's

c) ¯ fibrinolytic activity - ¯ levels of plasminogen activators

d) ¯ antithrombin III

Probably a protective adaptation to lessen the risks associated with the acute haemorrhage that occurs at delivery.

Increased risk of thromboembolic disease (Post-Anaesthesia ambulation )

Hematological changes

III : Other changes:

Leucocytosis up to 21,ooo/µL.

↑ ESR

10-20% ↓ in platelet count.(Mild thrombocytopenia not a contra-indication for neuraxial block).

Marked ↓ cell mediated immunity→ ↑ susceptibility to viral infection.

Metabolic Changes Pregnancy is

Diabetogenic

Human Placental lactogen(HPL)→ relative insulin resistance.

• Biochemically Starvation like state

↓ Blood Glucose & Amino Acid levels.↑ Free Fatty Acids, Ketones & triglycerides.

To promote fetal growth.

Insulin levels steadily rise during pregnancy

Secretion of HCG and elevated levels of estrogens promote hypertrophy of the thyroid gland.

↑ TBG (↑ T3 & ↑ T4) → Free T3, T4 & TSH

remain normal.

Metabolic Changes

• Increased level of relaxin - softening cervix

- relax symphysis pubis

- & pelvic joints

Increased risk of back pain(lax ligaments)

Musculo-skeletal changes

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Utero-placental Circulation

At term: uterine blood flow is 10% of CO≈ 600 – 700 ml/min.

80% to placenta 20% to myometrium

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Maximally dilates uterine vasculature so autoregulation is absent.

Uterine Blood Flow

Directly proportional to difference betweenuterine arterial and venous pressure.

Inversely proportional to uterine vascular resistance.

Uterine vasculature has abundant α-adrenergic & some β-adrenergic receptors.

Previously , vasoconstrictor agents with predominant β-adrenergic activity (e.g. Ephedrine) were of choice for hypotension during pregnancy.Recent studies show that α-adrenengic drugs (e.g.Phenylephrine) have similar effects causing less fetal acidosis.

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3 major factors ↓ uterine blood flow during pregnancy

SystemicHypotension

UterineVasoconstriction

Uterine Contractions

♦ Aortocaval compression.

♦ Hypovolemia.

♦ Sympathetic blockwith regional anesthesia.

♦ stress-induced endogenousCatecholamines during labor.

♦ α-adrenergic agonists.

♦ Hypertensive disorders→ generalized vasoconstriction.

♦ Labor.

♦ Oxytocin infusions.

♦ Extreme hypocapniaPaCO2 < 20 mmhg.

♦ Barbiturates &Propofol.

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Placental transfer of anaesthetic agents

Placental transfer of drugs depends on:

1) Molecular weight : < 500 Da cross easily.

2) Protein binding– inversely proportional

3) Lipid solubility: Highly ionized substances have poor lipid solubility.

4) Maternal & fetal pH : affect ionization of the drug.

5) Maternal drug concentration: affected by dose given and route of administration.

6) Timing of administration.

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Limited effects if < 1MAC & delivery within 10 min. of induction

Cross placenta freely

Inhalational Agents

Intravenous Agents :

Thipental, ketamine & propofolLimited fetal effects

in usual induction doses

(drug distribution, metabolism & placental uptake)

Variable effects. Cross placenta freely

Opioids

Most significant respiratory depressant

effects Morphine

Significant respiratory depression peaking 1- 3 hr after administration.

Meperidine

Minimal effect if < 1µg/Kg. Fentanyl

Minimal effects on fetus.

The highly ionized property impedes placental transfer.

Muscle Relaxants

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Local anesthetics → Placental transfer depends on:

1) pKa.

2) Maternal & fetal pH : Fetal acidosis → higher fetal to maternal

drug ratios . Binding of hydrogen ions to the nonionized form →

trapping

of local anesthetic in fetal circulation

3) Degree of protein binding : highly protein bound agents

diffuse poorly across the placenta.

Chloroprocaine has the least placental transfer as it is rapidlybroken down by plasma cholinestrase in the maternal circulation.

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Effect of labor on maternal physiology

Stages of labor

1st stage 2nd stage 3rd stage

Starts with true labor pains, ends by full cervical dilation.

Starts with full cervical dilation, fetal descent occurs, ends with complete delivery of fetus.

Extends from birth of the baby to delivery of theplacenta.

Latent phase Active phase

Progressive cervical effacement& minor dilataton (2 – 4 cm).

Progressive cervical dilatationup to 10 cm.

8 – 12 h in nulliparous5 – 8 h in multiparous.

Contractions are 1.5- 2 min apart, last 1 – 1.5 min

15 – 120 min.

15 – 30 min.

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Intense painful contractions

Maternal hyperventilation

MV ↑ up to 300%.

↑ O2 consumption 60% above 3rd trimester values

Marked Hypocapnia PaCo2 < 20 mmHg

Uterine VasoConstriction (fetal acidosis)

Periods of hypoventilation → transient maternal & fetal hypoxemia in betweenContractions.

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Each contraction

Displaces 300 – 500ml blood from uterus to central circulation.

COP ↑ 45% above 3rd trimesteric value.

Maximum strain on the heart occurs immediately after delivery.

Uterine intense involution→ sudden relieve of IVC→ ↑ COP 80% above prelabor values.

Summary To illustrate how all these changes may affect anaesthetic management, lets imagine performing a general anaesthetic for caesarean setion and list some key points

1) Careful attention to the assessment of the airway and any necessary preparation to deal with a potentially difficult airway in the pre operative period. 2)When positioning the patient on the table, remember to use either a left tilt of between 15 – 30 degrees on the table or a wedge under the right buttock to minimize aorto-caval compression.

3)Venous access often easier due to engorgement of the venous system

4) Pre oxygenation is essential and should be with a tight fitting mask for at least 3 minutes.

5) Rapid sequence induction with the application of cricoid pressure is mandatory. Intubation may be difficult and so adjuncts for difficult intubation should be available. 6) Once the airway is secured, ventilation should be aimed to keep the PCO2 in the normal range for pregnancy. 7) The MAC of volatile anaesthetic is slightly reduced. 8) There is decreased sensitivity to endogenous and exogenous catecholamines and so if vasopressors are required to maintain adequate blood pressure, the amounts needed may be greater. 10) Extubation should be done with the patient awake and on their side to reduce the risk of aspiration of gastric contents.