The state of pregnancy results in some fairly significant physiological changes in the mother. Some of these are driven by the hormonal changes, led by the placenta, whereas some are related to the increasing mass of the uterus and foetus. Many can be considered appropriate adaptive responses to the demand for supporting a rapidly developing foetus, and the process of delivery. However, some may lead to adverse effects when viewed in the context of modern medical therapy, and they are important to know about.
This is a systems based review of the changes.
These changes occur from the start of pregnancy to meet the demands of supply blood to the foetus, producing a hyperdynamic circulation. In summary:
Cardiac output increases by 30-50%
Stroke volume increase by 20-50% as the main cause of this
Heart rate increases by around 20%
Systemic vascular resistance decreases
There is an increase in total plasma volume of about 40-50% - approximately 2000ml
Red blood cell numbers only increase by around 20%, resulting in a dilutional anaemia.
Aortocaval compression can result in significant reductions in cardiac output when the patient is lying supine.
Cardiac output increases to provide the additional blood the foetus needs. This begins in the first trimester, continuing to result in an increase of about 30-50%. The initial change to trigger this is a reduction in systemic vascular resistance. This occurs at around 8 weeks gestation. To maintain an adequate systemic blood pressure, cardiac output is increased. This is initially primarily through an increase in stroke volume, and this remains the primary contributor throughout pregnancy, with an increase of 20-50% from baseline values. This increased stroke volume comes from both an increased end-diastolic volume (EDV) and an increase in myocardial muscle mass. The increased EDV is linked to the ongoing increase in total plasma volume that occurs. This is brought about by the renin-angiotensin system, leading to an overall increase in plasma volume of around 40-50% - a total blood volume of around 2000ml. Of note, the increase in red blood cell (RBC) numbers only increases by around 20% in this timeframe, and thus results in the dilutional anemia of pregnancy. Alongside this increase in stroke volume there is also an increase in heart rate which contributes to an increased cardiac output, an increase of about 20%.
Significant cardiovascular changes occur in late pregnancy related to the mass of the uterus. This causes compression of the inferior vena cava (IVC) reducing venous return and thus cardiac output (although there is some compression of the descending aorta as well). This can occur from 20 weeks gestation, primarily when the mother is in the supine position. The impact on cardiac output can be a reduction by as much as 25-30%. As such, a degree of left lateral tilt or lateral uterine displacement is needed in mothers who are lying supine to reduce this impact on cardiac output.
These changes can result in changes to the clinical findings and investigations of patients. On heart auscultation there can be splitting of the first heart sound, an S3 sound, and a soft ejection systolic (flow) murmur. The heart is displaced superiorly and laterally, with subsequent changes visible on a CXR. There will also be changes to the ECg from this, with a left change in axis of 15-20 degrees. There can also be T wave inversion in the lateral leads and lead III, mimicking hypertrophic changes. Despite the changes in volumes, the central venous pressure isn’t changes. Peripheral vasodilation will generally produce nicely dilated veins, facilitating cannulation.
Labour and delivery are also associated with cardiovascular changes. The pain and sympathetic stimulation of labour increase cardiac activity. There is also a process of autotransfusion with delivery (although also a clear risk of some blood loss). Both of these factors can put stress on a cardiovascular system which is susceptible e.g. mothers with significant cardiovascular disease. Of note, contractions result in an autotransfusion of approximately 500ml, as blood is expelled from the uterus. This is relevant as it can result in increased size of the epidural veins, increasing the chance of a vessel puncture if the procedure is continued during contractions.
It is important to remember about the uteroplacental circulation. This receives about 20% of the maternal cardiac output. It has no autoregulatory properties and so is susceptible to changes in the mother’s circulation e.g. from vasoactive drugs.
A gradual return to normal values occurs in the 6 to 9 weeks postpartum.
Hypercoagulable state - brought about by generally increased clotting factor levels
Stable platelet levels, with slight drop towards the end
Pregnancy leads to a hypercoagulable state. Evolutionarily this is to reduce the bleeding that occurs at the time of delivery, and placental separation. However, this leads to a 10 fold increase in venous thromboembolic disease during pregnancy.
The changes are an increase in the number of nearly all clotting factors. Only factors XI and XIII don’t increase. There is an especially notable increase in levels of fibrinogen and factor VII. There is also a decrease in the activity of antithrombotic factors, and of fibrinolysis.
Platelet levels are generally fairly stable through most of pregnancy. There is an increased degree of production, but this is offset by the haemodilutional effects of increased plasma volume, and increased destruction. This consumptive element is generally more notable in the later stages of pregnancy, and so a drop in platelet levels in the third trimester is common. There is usually no significant functional impact of this. However, there is some discussion about the levels at which neuraxial blockade can safely be performed at, with 75,000x10^9/L commonly being used as a cut off.
As noted above, the increase in plasma volume results in a haemodilutional anaemia, despite an increase in the number of RBCs as well. This does not have a notable impact on oxygen transport, due to compensation by an increased cardiac output and rightward shift of the oxygen dissociation curve.
The main changes are:
An increase in minute ventilation of 45% - primarily due to an increase tidal volume.
The FRC is reduced by 20% at term due to pressure from the uterus.
The increased metabolic activity of a growing foetus results in an increase in oxygen uptake and CO2 production. As such, there is an increase in ventilation to allow for this. Minute ventilation in pregnancy increases by around 45%. This is primarily due to an increase in tidal volume, with little change in respiratory rate. The main driver for this is the effect of progesterone to increase the sensitivity of the respiratory centre to CO2. The increased ventilation results in a reduced PaCO2 of around 4 kPa, which undergoes metabolic buffering so that the pH remains normal.
The expansion of the uterus pushes upwards, resulting in elevation of the diaphragm, and subsequently reducing the functional residual capacity. This can be by 20% at term, and more when the mother is lying supine. The consequence of this is a risk of rapid desaturation at the onset of apnoea when undergoing a GA.
Capillary engorgement leads to mucosal swelling in the mother’s airway. This can be another factor that contributes to difficulty in intubation, and is recognised that standard tools of airway assessment (e.g. Mallampati score) have less predictive value in this population. The mucosal engorgement means that trauma to airway tissues is more likely, and care airway manipulation is important. There is also an increased incidence of epistaxis with nasal instrumentation because of this, and so the nasal route should be avoided.
There is decreased lower oesophageal tone and increased reflux in pregnancy
Gastric motility is decreased in labour (though unclear in normal pregnancy)
There is a subsequent increased risk of aspiration with general anaesthesia.
Some of the effects of pregnancy and labour on the GI tract are controversial. Progesterone has a relaxing effect on smooth muscle, including the lower oesephageal sphincter, and possibly some effect on general gut motility. The impact of this, and the mass effect of the gravid uterus, increases the incidence of reflux (and commonly symptomatic heartburn) in pregnancy. Whether gastric emptying is delayed in normal pregnancy is not certain. However, it is clear that labour, and the associated sympathetic stimulation and pain, do delay gastric emptying. Opioids around this time probably also contribute. The consequences of this are an increased risk of aspiration with general anaesthesia, particularly if required as an emergency during labour. This risk probably particularly increases at around 16 weeks gestation.
GFR increases by about 50% due to the increase cardiac output
Clearance of drugs and normal metabolic products is increased
The increased cardiac output also results in increased renal blood flow. This results in an increase in glomerular filtration (an increase of about 50% from around 100ml/min to 150ml/min). This results in a increased clearance of both metabolic products (urea and creatinine) and drugs. As such, renal markers at the high end of ‘normal’, can signify renal disease in a pregnant patient. This increased filtration can push the limits of the tubular reabsorption, and so a small degree of glucose and protein in the urine is a normal finding. The upper limit of normal for protein loss is 300mg/day.
Liver enzyme levels mostly decrease, though ALP levels increase.
Liver enzyme levels are usually slightly reduced in pregnancy. An exception is alkaline phosphatase (ALP) which is produced by the placenta. Elevated liver enzymes can be an indication of pathology in the pregnant patient e.g. HEELP syndrome. Plasma cholinesterase levels are usually reduced, reaching a nadir just after term (as low as 33% normal). This is due to reduced liver production and haemodilution but the effects on drugs that rely on these enzymes in not noted as significant in the majority of patients.
Central Nervous System
Pregnant patients have an increase sensitivity to neuraxial anaesthesia - needing a dose of around 25% less
They also have an increased sensitivity to general anaesthetic agents, with a MAC reduced by around 30%
Pregnant patients have an increased sensitivity to neuraxial anaesthesia. Diverted blood (due to resistance in the IVC) flows through the epidural veins, engorging them. As this space is fixed, there is a compensatory reduction in CSF. There is also an increased neuronal sensitivity to local anaesthetic agents. Both these factors reduce the dose of neuraxial anaesthetic agent needed in the pregnant patient by about 25%.
There is also an increased sensitivity to general anaesthetic agents. The MAC in pregnant patients is reduced by around 30%. The reason for this is multifactorial, though there is some impact of the hormonal changes of pregnancy e.g. progesterone.
Links & References
Bedson, R. Riccoboni, A. Physiology of pregnancy. CEACCP. 2014. 14(2):69-72
Birnbach, D. Browne, I. Anaesthesia for obstetric, in: Miller’s Anaesthesia (7th ed).
Heazell, A. Clift, J. Obstetrics for anaesthetists. Cambridge University Press. 2008.