Physiological Changes in the Pregnancy and Anesthetic Implication during Labor, Delivery, and Postpartum

3.1. Changes Related to Cardiovascular System

Early in pregnancy, physiological changes occur, resulting in overall hyperdynamic circulation. As early as 8 weeks of pregnancy, peripheral vasodilation and a decrease in systemic vascular resistance (SVR) occur as a result of elevated levels of oestrogen and progesterone [22, 23]. Because the uteroplacental circulation lacks autoregulation, cardiac output (CO) must rise to maintain blood pressure (CO × SVR) [24]. If arterial pressure (AP) is to be maintained, which is necessary for a well-functioning uteroplacental unit, cardiac output (CO) must be increased. During pregnancy, cardiac output increases by 30-40%, with the largest increase occurring around 24 weeks of pregnancy [25]. This is accomplished initially by increasing stroke volume (SV), but as the pregnancy proceeds, the increase in SV plateaus, and the heart rate rises. This rise in CO is achieved in early pregnancy by increasing the heart rate (HR) by 15-25 percent, followed by a 20-30 percent increase in stroke volume (SV) [26]. Heart rate rises quickly (before the end of the first month of pregnancy) and then plateaus at 10-15 beats per minute by 28-32 weeks of pregnancy. On the other hand, stroke volume increases by the mid-first trimester and continues to rise during the second trimester, with the increase in SV due to an increase in both end-diastolic volume (EDV) and ventricular muscle wall mass. The increased blood volume, which increases from 6 to 8 weeks gestation to a maximum amount at 32 weeks, causes increased preload and EDV. When compared to a nonpregnant person, there is a total increase in blood volume of up to 2000 ml. As a result, the pregnant patient is able to adjust for blood loss effectively [27]. Beginning at 6 to 8 weeks of pregnancy, blood volume increases to roughly 20% by the mid-third trimester [28]. The renin-angiotensin system is activated by a wide pulse pressure and low mean arterial pressure, which causes salt and water retention. This causes a 40-50 percent rise in plasma volume. Furthermore, echocardiography showed increased end-diastolic chamber size and total left ventricular wall thickness but no change in end-systolic volume, indicating an increase in ejection fraction.

The heart is also shifted cephalad and laterally due to anatomical alterations caused by a gravid uterus. In both cephalad and lateral directions, the heart is physically dilated and displaced. A healthy pregnancy ECG with 15-200 degrees of left axis deviation and inverted T waves in the lateral lead and lead III can simulate left ventricular hypertrophy and other structural diseases [29]. Because of the gravid uterus' gradual elevation of the diaphragm, the heart is shifted to the left and upward throughout pregnancy. Sinus tachycardia or benign dysrhythmias, depressed ST segments and flattened T waves, left axis deviation, and left ventricular hypertrophy can all be seen on the electrocardiogram of normal parturients. Auscultation typically reveals a tricuspid or mitral regurgitation systolic murmur, as well as a third or fourth heart sound. Cardiac output, heart rate, and stroke volume recover to prelabor levels 24-72 hours after birth and to nonpregnant levels 6-8 weeks later [30]. (Table 1) lists the changes in cardiac auscultation and electrocardiogram [31].

The uterus, kidneys, and skin get the majority of the rise in CO, which is used to feed nutrition to the foetus, eliminate maternal and foetal waste products, and aid in maternal temperature control, respectively [32-34]. However, the cardiac output varies depending on the size of the uterus and the position of the mother at the time of measurement. The pressures in the femoral venous and inferior vena caval are significantly higher in normal pregnant women. Atrial filling is maintained by collateral vessels, although veins, notably the epidural venous (Batson's) plexus, are engorged [22]. Due to myocardial remodeling during pregnancy, filling pressures (CVP, pulmonary capillary wedge pressure, LV end-diastolic pressure) stay unchanged despite enlarged heart dimensions [35].

While the pregnant lady is in the supine posture, the enlarged gravid uterus might produce aortocaval compression and diminished ventricular filling, resulting in an underestimate of cardiac performance (Fig. 1). The iliac veins combine to produce the inferior vena cava at a level that corresponds to the L4/5 interspace anatomically. Inferior vena cava compression may occur after the uterus reaches this level. The mechanical consequences of the expanding uterus can produce compression of both the inferior vena cava and the descending aorta in the supine position by the time the uterus hits the level of the umbilicus, which corresponds to 20 weeks in a singleton pregnancy. The combination of these factors results in a lower venous return and a lower CO level [36]. When turning from the lateral to the supine position at 38-40 weeks gestational age, CO drops by 25-30 percent.

Because the uteroplacental circulation lacks autoregulation, this results in lower uterine blood flow and placental perfusion. Additionally, systemic vascular resistance is reduced by roughly 20%. During a normal pregnancy, blood pressure does not rise, and systolic and diastolic blood pressures decrease by about 8% and 20%, respectively [35]. The reduction in blood pressure reported despite an increase in cardiac output could be due to pregnancy hormones (estradiol and progesterone), prostacyclin, and nitric oxide. As a result of aortocaval compression, maternal hypotension and consequent foetal deterioration (acidaemia) might occur [24]. Increased sympathetic tone causes vasoconstriction and tachycardia, and blood flow from the lower limbs is diverted through the vertebral plexus and azygos veins to reach the right heart are among the maternal compensatory mechanisms for aortocaval compression. These compensatory processes may be insufficient in many parturients to maintain blood pressure in the supine posture, resulting in supine hypotension (or aortocaval compression syndrome) [37, 38]. Pallor, transitory tachycardia followed by bradycardia, perspiration, nausea, hypotension, and dizziness in the supine posture are all symptoms that are eased by shifting to the side. It can cause unconsciousness or maternal death in its most severe form [24]. Even if the mother is asymptomatic, the mother's uterine blood flow may be hampered [36].

During labor, however, cardiac output increases even more, up to 50% greater than prelabor levels, despite the fact that adequate analgesia can mitigate some of this increase. Cardiac output rises to a maximum of 80 percent above prelabor levels and around 150 percent above nonpregnant levels in the early postpartum period. The higher cardiac output is maintained by an increase in stroke volume as well as heart rate. Despite the higher CO, there is a transitory drop in AP, resulting in wider pulse pressure and lower mean arterial pressure. This activates the renin-angiotensin system, causing water and salt retention and, as a result, an increase in plasma volume [36]. The changes in CO during labour and the postpartum period are summarized in (Fig. 2) [39, 40].

3.2. Clinical Implications Related Anaesthesia

The apical impulse is moved laterally and cephalad to the fourth intercostal space due to structural alterations. Increased blood volume provides some reserve for normal blood loss during delivery (300-500 mL for vaginal delivery, 600-1000 mL for caesarean delivery) and peripartum haemorrhage. However, because of this increase in blood volume, pregnant women may not show signs and symptoms of hypovolemia until roughly 1500 ml of blood has been lost [24]. More than 1500 ml of blood may have been lost by the time the usual symptoms and signs of hypovolaemia, such as tachycardia, hypotension, and oliguria, appear [27].

Venepuncture and i.v. cannulation are much easier with peripheral vasodilation. During epidural anaesthesia, epidural veins enlarge, increasing the risk of intravascular injection—also known as a “bloody tap.” This is compounded by the fact that 500 ml of blood is discharged from the uterus into the maternal circulation during uterine contractions. In the event of hypotension, greater doses of vasopressors such as phenylephrine are necessary due to the downregulation of adrenergic receptors. I.V. and inhalation anesthetics, which cause a decrease in SV and CO, as well as neuraxial block, which causes sympathetic block, all enhance the risk of supine hypotension. Supine hypotensive syndrome can be aggravated by a reduction in SV and CO during general anaesthesia (GA) and sympathetic suppression during neuraxial anaesthesia. As a result, the supine position should be avoided or the uterus displaced laterally with a wedge under the hip. Once the foetal head is engaged, the negative effects of aortocaval compression are reduced. The Oxford position has been found to have better haemodynamic stability, more reproducible block height, and prevented aortocaval compression during neuraxial anaesthesia. It is a modified lateral position with an upward slope in the thoracic region, with no supine position allowed until surgery starts. If the left lateral tilt is used in the event of cardiac arrest and cardiopulmonary resuscitation, it must be done with the parturient on a firm, flat surface to allow for effective chest compression. If this is not possible, the supine position with manual uterine displacement must be used [41]. Pain and auto-transfusion add to the cardiac workload during labor and delivery. In the second stage of labor and the early postpartum period, parturients with a low cardiac reserve are at a higher risk of ventricular failure and pulmonary oedema. Early in labor, regional analgesia should be used and then gradually reduced after delivery. It is also worth noting that incipient cardiac disease is a leading cause of maternal death in the United Kingdom. Many of the initial symptoms and signs are ‘soft' and are mistakenly attributed to pregnancy's physiological changes. Maintain a high level of suspicion, and if there is any doubt, additional investigations and cardiology referrals should be considered [42]. Pregnant women with valvular heart disease (e.g., aortic or mitral stenosis) or coronary artery disease may not tolerate increased cardiac output. Myocardial decompensation can occur as early as 24 weeks of pregnancy, during labor, and especially soon after delivery. The risk of intravascular catheter placement in pregnant women is increased by engorgement of the epidural venous plexus; the direct connection of the azygos system to the heart and brain also increases the risk of local anesthetic cardiovascular and central nervous system toxicity [43].

3.3. Changes Related to Hematological System

During pregnancy, the volume of the mother's blood increases, which includes an increase in plasma, red blood cells, and white blood cells [44]. While the increase in plasma volume is around 40-50%, the increase in red blood cell mass is only around 15-20%. Dilutional physiological anemia (normal hemoglobin 12 g/dL; hematocrit 35) is caused by a discrepancy in the increase in plasma volume and red cell mass during pregnancy [28]. Blood viscosity is reduced by about 20% as a result of this hemodilution. A lower haematocrit lowers blood viscosity and blood flow resistance in the uteroplacental circulation [24]. The exact mechanism of this increase in plasma volume, on the other hand, is unknown. Several mediators are considered involved, including renin-angiotensin-aldosterone, atrial natriuretic peptide, estrogen, progesterone, and nitric oxide. The most likely explanation is that the increase is due to a “underfill” state caused by initial vasodilation, which causes fluid retention by stimulating hormones like renin, angiotensin, and aldosterone [45]. Alternatively, some have proposed an “overfill” state characterized by an early increase in sodium retention (due to an increase in mineralcorticoids) followed by fluid retention, resulting in an increase in blood volume and then vasodilation. As uterine contractions squeeze blood out of the intervillious space and into the central circulation during labor, blood volume increases even more. After delivery, the uterus involutes and placental circulation ceases, resulting in a blood autotransfusion of approximately 500 mL. The leukocyte count gradually rises to around 15,000 cells per millimeter [32]. This may increase during labor and delivery, but it is not a sign of developing sepsis. Polymorphonuclear cells, which are dysfunctional, play a major role in this increase. Because sepsis is a state of altered immune competence (allowing for paternal antigens in fetoplacental tissue), pregnant patients are predisposed to developing it [36]. This explains why infections are more severe, but it does not mean that parturients are more susceptible to infections [46]. The production of autoantibodies and the levels of immunoglobulins A, G, and M are unaffected [24].

All clotting factors (except XI and XIII) and fibrinogen increase during pregnancy, while natural anticoagulants decrease and fibrinolytic activity decreases [47]. Standard clotting screens do not usually reflect the changes that occur. The overall effect of these changes is variable, but prospective observations have shown that platelet count decreases as pregnancy progresses, with 7.6% of women having a count less than 150,000 and 1% having a count less than 100,000 at term [48]. Platelet production and thrombopoietin levels are also increased [49], and platelet aggregation measured in vitro is likewise increased; indices of platelet destruction are also increased. Although platelet production increases, the count does not increase due to increased destruction and haemodilution. The platelet count, on the other hand, drops as a result of increased destruction and haemodilution, which occurs at its peak in the third trimester. Platelet count decreases (90,000-100,000) in a minority of women, which is normal (gestational thrombocytopaenia) and resolves in the postpartum period [50]. With an increased risk of thromboembolism during pregnancy (10 times) and postpartum, the coagulation and fibrinolytic pathways are altered (25 times). In a normal pregnancy, endogenous anticoagulants such as protein S are reduced, and activated protein C resistance is acquired throughout pregnancy, adding to the prothrombotic condition. Placental-derived plasminogen activator inhibitor (PAI) impairs fibrinolysis throughout normal pregnancy, but it returns to normal when the placenta is delivered [51]. As a result of the physiologic changes, pregnancy becomes hypercoagulable [52]. Prothrombin time and activated partial thromboplastin time have both been reduced by 20%. There are also higher levels of fibrin breakdown products and plasminogen [53]. The hypercoagulable state lasts for 5-7 days after delivery, with a higher risk of thrombotic problems, before reverting to baseline by 2 weeks.

3.4. Clinical Implications Related Anaesthesia

Increased blood volume and improved coagulation serve two key functions: (1) they meet the increased circulatory needs of the expanding uterus, fetus, and placenta, and (2) they protect the parturient from bleeding during birth [43]. When deciding on fluid and blood replacement in the peripartum phase, anesthesiologists should take into account the increased blood volume. Parturients become hypercoagulable as their pregnancy advances, putting them at risk for thromboembolism.

Blood volume gradually returns to normal over 8 weeks after a fast mobilization and diuresis of some fluid in the first few postpartum days [43]. During the antenatal period and again upon admission to the hospital, all pregnant women should have their thromboembolic risk assessed and appropriate thromboprophylaxis administered. Because low molecular weight heparins (LMWHs) are increasingly being utilized in the antenatal period, it is critical that the anesthesiologist is informed of this, as well as the time since the last dose, as regional blocks should not be performed within 12 hours after a prophylactic LMWH dose [54]. In an otherwise healthy parturient, platelet counts are usually within normal ranges, and the results of a platelet count are not required prior to regional anaesthesia.

The platelet count can drop fast in severe preeclampsia, putting the parturient in danger of an epidural haematoma. A recent platelet count (within 6 hours) should be conducted both before sitting an epidural and before withdrawing the epidural catheter for the group of patients whose condition is considered severe enough for the Collaborative Eclampsia Trial regimen of magnesium sulphate [55]. There is no one platelet level that predicts the development of neuraxial haematoma; platelet number and function are both relevant. However, testing for both platelet count and function is recommended (aggregability). In an emergency, laboratory testing might take a long time, therefore, thromboelastography can help assess the entire coagulation process (initial fibrin plug creation, platelet aggregation, clot strengthening, and fibrinolysis) [56]. TEG (thromboelastography) is a point-of-care bedside test that determines global haemostatic function. TEG monitors the entire coagulation process, from fibrin production to platelet interaction, clot strengthening, and fibrinolysis. Platelet function is shown by the maximum amplitude (MA). In the presence of thrombocytopenia and aberrant TEG, most anaesthetists will not deliver regional anaesthesia [55].

3.5. Changes in the Respiratory System

As early as the fourth week of pregnancy, changes in respiratory parameters begin. To meet the metabolic demands of the mother and fetus, anatomical and physiological changes occur. Oxygen consumption and carbon dioxide generation rise by about 60% compared to prepregnancy levels. By the second trimester, there has been a 45 percent increase in minute ventilation due to an early increase in tidal volume [57]. At term, minute ventilation is raised by around 50% over nonpregnant levels. The increase in minute ventilation is mainly due to an increase in tidal volume (40%) and, to a lesser extent, an increase in the respiratory rate (15%) [58]. There is a corresponding increase in alveolar ventilation.

Progesterone acts as a respiratory stimulant, making chemoreceptors more sensitive to carbon dioxide (CO₂) [59]. PaCO₂ decreases to 30-32 mmHg in the first trimester and remains in this range throughout pregnancy because of increased CO₂ production (about 300 ml/min) and higher MV. End-tidal CO₂ and PaCO₂ do not have a gradient. The increase in ventilation leads to decreased arterial carbon dioxide tension with an average PaCO₂ of 4 kPa at term. In active labor, this can be reduced even more. This would normally result in respiratory alkalosis, which is somewhat mitigated by lowering serum bicarbonate levels to around 20-21 mEq/L and a pH of 7.42-7.44. Although renal bicarbonate excretion keeps arterial pH stable, PCO₂ drops to 32-35 mmHg at term. Even before a rise in metabolic rate, increased progesterone concentrations during pregnancy are likely to drive increased respiration [60].

Early in pregnancy, PaO₂ rises due to a decrease in PCO₂. Progesterone is the primary force behind this, as it reduces the respiratory center's carbon dioxide response threshold. PaO₂ rises during pregnancy as a result of increased alveolar ventilation; however, after mid-gestation, PaO₂ declines in the supine position when functional residual capacity (FRC) falls below the closing capacity, resulting in airway closure during tidal volume breathing. The diaphragm is pressed in a cephalad direction as the uterus swells. In the upright posture, the functional residual capacity (FRC) is reduced by 20%, while in the supine position, it is reduced by up to 30% (Table 2). At the end of the term, the functional residual capacity, expiratory reserve volume, and residual volume are all reduced (Fig. 3). These alterations are due to the diaphragm's cephalad displacement caused by the big gravid uterus. Because of the rise in tidal volume and inspiratory reserve volume, the inhalatory capacity increases slightly. The vital ability remains the same. Because of the increase in chest circumference, total lung capacity is only slightly diminished. The closing capacity (CC) remains unchanged, but the decrease in FRC contributes to an earlier desaturation by allowing lung volume to go below CC more quickly. The rightward shift in the maternal oxygen dissociation curve increases oxygen delivery to the foetus, and the P50 value rises at term (30 vs. 26 mmHg). The P50 of fetal haemoglobin is around 18 mmHg, indicating that it has a stronger affinity for oxygen. Despite the diaphragm cephalad displacement, diaphragm excursion during breathing increases by 2 cm while chest wall excursion decreases.

Flow volume loops show no change as a result [61]. Due to increased metabolic demand, MV increases by 70-200%, PaCO₂ drops to 10-15 mmHg, and oxygen consumption rises by 40-75% during labor. By 6-8 weeks after delivery, MV, TV, and oxygen consumption return to prepregnancy levels. Within 6-12 weeks after delivery, all other respiratory indicators revert to prepregnancy levels. Following the reduction in uterine size, FRC alterations return to normal 1-2 weeks postpartum.

Pregnancy causes anatomical changes as well. The mucous membranes of the lungs become vascular, edematous, and friable. Capillary engorgement of the nasal, oropharyngeal, and laryngeal mucosa occurs as a result of oestrogen's impact. Anteroposterior and transverse diameters of the chest wall grow by 2 cm each, resulting in a 5-7 cm rise in circumference [23]. As the tidal volume rises, alveolar ventilation rises dramatically, with no change in the ratio of dead space to tidal volume (VD/VT). During pregnancy and labor, the voice may deepen, and the Mallampati score rises gradually [62].

3.6. Clinical Implications Related Anaesthesia

The majority of pregnant women feel physiological breathlessness, but it can also be the presenting symptom of serious underlying respiratory or heart problems. Breathlessness that comes on suddenly or is accompanied by chest pain, orthopnoea, and paroxysmal nocturnal dyspnea are all signs of a more serious condition [36]. Despite appropriate pre-oxygenation, a lower FRC and higher oxygen demand can result in fast desaturation during apnoea [63]. Reduced FRC also reduces denitrogenation time and speeds up the uptake of inhaled anesthetics. Gas exchange at the alveolar level is facilitated by greater minute breathing and a lower FRC, resulting in a faster rate of inhalation agent uptake and changes in depth of anaesthesia. When ventilating a parturient, keep in mind the lower levels as well as the comparable gradients between end-tidal CO₂ and PaCO₂. The lack of gradient is attributed to a reduction in alveolar dead space (increased blood perfusion from an increase in maternal CO). Hyperventilation should be avoided since it can lead to respiratory alkalosis and a left shift in the oxygen dissociation curve, which means less oxygen gets to the fetus. Because of decreased uteroplacental perfusion due to uterine vasoconstriction and tilting of the maternal oxygen dissociation curve to the left, maternal alkalosis along with decreased PaCO₂ values as a result of hyperventilation as a result of labor pain can cause fetal acidosis. Uncontrolled mother discomfort during labor can raise metabolic needs even further, resulting in an increase in maternal lactate levels, indicating that oxygen demands are greater than supply. In the absence of pain medication, minute volume increases even more during labor and PCO₂ may drop to 17 mmHg. Despite a better response to hypoxic ventilator drive, a vulnerable parturient's higher oxygen demand cannot be met without the use of supplemental oxygen. Although opioids help to mitigate this alteration, epidural analgesia is advantageous since it lowers metabolic demands during labor [64]. Even in the context of good regional analgesia, maternal expulsive attempts boost breathing in the second stage [65, 66].

Anatomically, capillary engorgement causes swelling and friability of the nasopharyngeal and oropharyngeal tissues. Because of the increased risk of epistaxis during pregnancy, the nasopharyngeal approach should be avoided due to increased edema, vascularity, and friability of the mucous membrane. The airway of the parturient can become obstructed, making tracheal intubation more difficult. The Mallampati class is still widely used to predict intubation, but it has been demonstrated to have a low positive predictive value. When combined with other difficult airway predictors, it can be quite beneficial. During pregnancy, and especially during labor, the Mallampati categorization deteriorates [62]. The Mallampati score can alter depending on the stage of labor, with the greatest increase in Mallampati 3 and 4 grades occurring between the first and second phases [67]. This, combined with larger breasts and rising obesity rates among pregnant women, can make laryngoscopy more challenging. In tough situations, laryngoscopes with short handles, smaller diameter endotracheal tubes, and a ramp position at the head end may be required.

4.1. Clinical Implications Related Anaesthesia

Gastric emptying is not delayed in the non-laboring term parturient. The fasting guidelines, on the other hand, do not need to be changed. Regardless of when they last ate, pregnant women in labor should always be regarded as having a full stomach. Gastric emptying is delayed in the laboring patient, who may be experiencing cumulative effects from anxiety and labor pain. Women who have taken opiates by any route, including epidural or subarachnoid, experience a delay in gastric emptying [76]. As a result of the increased intra-abdominal pressure and reduced LOS tone, there is a higher risk of aspiration of gastric contents. During general anesthesia and intubation, the risk is raised. When general anesthesia is unavoidable, conventional precautions (quick sequence induction and endotracheal intubation) should be used instead [43]. Preference for neuraxial procedures and the use of aspiration prophylaxis are two more essential stages in prevention. Before a cesarean section or the induction of regional anesthesia, it is critical to use a nonparticulate antacid on a regular basis and to allow for optimal mixing of the antacid and stomach contents. Aspiration causing Mendelson's syndrome (acid aspiration generating an inflammatory response in the lung parenchyma resulting in chemical pneumonia) is becoming less common. Pregnant women who are not in labor or have no other risk factors for aspiration may not need to be treated. A moderate dose of clear fluid is advised in simple labor [77]. Oral intake during normal labor, on the other hand, is a contentious topic. The safest and most successful technique for preventing aspiration is to employ a regional anaesthetic [36]. Antacid premedication should be recommended for all patients starting at 16 weeks of pregnancy. When histamine H₂-receptor antagonists are combined with sodium citrate, the mean pH rises and the percentage of patients with a gastric pH < 2.5, which is essential for chemical pneumonitis, falls. If general anaesthesia is required, a rapid sequence induction approach with cricoid pressure and a cuffed tracheal tube should be employed following preoxygenation. Gastrointestinal effects return to prepregnancy levels 24-48 hours after delivery.

Despite a decrease in plasma cholinesterase, a single dosage of succinylcholine does not have a clinically meaningful impact on prolonging. This is most likely owing to increased distribution volume and decreased sensitivity [24]. However, to increase sensitivity to succinylcholine, the activity must be reduced by 50%; therefore, medication doses must be modified.

Around 11% of postpartum women have clinically inadequate activity, which manifests as an increased reaction to typical succinylcholine dosages. Even with this decreased activity, when general anesthesia is required, regular succinylcholine dosing for intubation is suggested, although the use of a peripheral nerve stimulator seems reasonable. However, if the parturient has HELLP syndrome, caution should be exercised because more than 60% of these individuals have pseudocholinesterase activity below the normal range [78].

5.1. Clinical Implications Related Anesthesia

In parturients, normal nonpregnant BUN and Cr levels indicate impaired kidney function. Urinary protein excretion of more than 300 mg per day should be investigated further [81]. Because the normal range of serum creatinine in pregnant women is lower, a little increase in readings suggests a bigger loss in renal function. Low albumin levels cause highly protein-bound medicines, including digoxin, midazolam, thiopentone sodium, and phenytoin, to become more free [23]. Aldosterone's effects are heightened, resulting in increased water absorption and a rise in the volume of distribution and elimination half-life of certain medications, such as thiopental.

Although the primary renal disease is uncommon, renal function impairment is evident in more frequent pregnant diseases such as preeclampsia. Renal impairment necessitates a cautious anesthetic strategy that includes careful hydration management, diabetes control, and medication dose and protocol adjustments [24].

6.1. Clinical Implications Related Anaesthesia

Airway evaluation, ECG, invasive cardiovascular monitoring, treatment of hydration, electrolyte and glucose imbalance, and avoidance of sympathetic stimulation are all required for a parturient with thyrotoxicosis. Care should be provided in a critical care setting, with postpartum monitoring continuing. Pathological conditions resulting from iodine deficiency, hypothyroidism, or hyperthyroidism are important in anaesthesia and should be addressed with the physiological changes of pregnancy in mind. In patients with autonomic dysfunction due to diabetes mellitus or diabetic ketoacidosis, GA can disguise the signs and symptoms of hypoglycemia, while neuraxial anaesthesia can cause exacerbated haemodynamic instability [24].

7.1. Clinical Implications Related Anaesthesia

As pregnancy advances, the anatomy and sensitivity to pain and medication change. Parturients are also more vulnerable to medicines that affect the central nervous system, with a 30% reduction in the MAC of inhalation anaesthetics [91]. Intravenous induction and sedative drugs are physiologically more sensitive in pregnant women [92]. Increased venous pressure below the gravid uterus causes blood to flow down the path of resistance, diverting it into the engorged epidural plexus.

When the epidural space is occupied, the volume of cerebrospinal fluid decreases to compensate. When compared to the nonpregnant state, this, combined with increased neural susceptibility to local anaesthetics and a higher apical level of thoracic kyphosis, results in a 25% reduction in the dose requirement for spinal and epidural anaesthesia, with a faster onset and longer duration of action. Since the conclusion of the first trimester, the spinal dose of local anaesthetic (LA) has decreased by 25-40%, indicating that changes in epidural space anatomy are not the main cause. Progesterone has been discovered to improve the susceptibility of neuronal membranes to LA [93]. Even though the specific mechanism of increased sensitivity of the central nervous system and peripheral nervous system to general and local anesthetics is unknown, it is generally recommended to reduce anesthetic doses in pregnant women, at least at first. It is unknown when these modifications revert to their nonpregnant condition due to a lack of evidence and confusion about the actual processes behind the heightened local anesthetic sensitivity during pregnancy. The sensitivity to spinal anesthetics appears to be normal 24-48 hours after delivery. Following sympathetic blockade caused by neuraxial anaesthesia, pregnant women are more susceptible to hypotension and haemodynamic instability. In isolated nerve fibers, enhanced sensitivity to bupivacaine has also been reported [94]. The enhanced susceptibility of the peripheral nervous system to anesthetics reported in parturients could be due to progesterone or one of its active metabolites. This enhanced sensitivity was also seen in nerves from oophorectomized rabbits who had been given exogenous progesterone for a long time [93]. Surprisingly, this behavior was not observed after acute progesterone intake [95]. Peripheral nerve sensitivity to local anesthetics has also been demonstrated in humans [96].

8.1. THE FIRST TRIMESTER

Physiological factors are significantly altered during pregnancy, altering normal reactions to anesthetic effects. The physiological changes in numerous organs during pregnancy are an adaptive response to the altered metabolic profile and the many demands and stresses that come with pregnancy. During the first trimester, the main goal is to prevent any substance or method that may interfere with appropriate embryological development. Because physiological functions are significantly altered after 6-8 weeks, oxygenation, normovolaemia, and stable haemodynamic parameters are the primary goals of anaesthetic administration at this time [4]. As an adaptation response, these physiologic alterations influence nearly all major organ systems, including the cardio-vascular, pulmonary, renal, hepatic, and neurological systems, and result in multiple metabolic changes [4]. Increased oxygen consumption is required to meet the increased demands of both maternal and foetal tissues, while a parturient's functional residual capacity is diminishing, making more prone to hypoxemia. Normal pregnant hyperventilation causes CO₂ to be washed away, resulting in relative hypocarbia. Reduced minimum alveolar concentration, faster inhalational induction due to decreased functional residual capacity, rapid induction with soluble agents, and increased risk of hypoxemia due to decreased functional residual capacity and increased oxygen consumption are some of the notable and significant anaesthetic implications during this time [62]. Excessive mechanical breathing during GA might result in a drop in CO₂, which causes severe vasoconstriction, lowering maternal cardiac output and jeopardizing uterine blood flow.

Titration of anaesthetic medications is essential because the requirements for both inhalational and intravenous drugs are reduced throughout this time. Increased blood plasma and RBC volume; increased cardiac output; increased heart rate; and benign arrhythmias such as ST, T, and Q-wave alterations, with left axis deviation in some parturients, are among the noteworthy cardiovascular abnormalities [97, 98]. The purpose of anaesthetic management is to distinguish these alterations from those caused by overt cardiac diseases such as systolic murmur (>grade III), diastolic murmur, and severe symptomatic arrhythmias.

Hormonal changes during pregnancy, in addition to the aforementioned alterations, might result in greater weight gain and vascularity. Breast enlargement, laryngeal oedema, and increased chest antero-posterior diameter damage the soft tissues of the neck, making airway management difficult. The oro-nasal airway must be meticulously instrumented due to the increased vascularity of the mucous membranes, which poses a greater risk of bleeding. Because plasma cholinesterase levels are reduced in more than 30% of parturients, patients given GA and succinylcholine may need to be ventilated for longer periods of time. Patients with a significant drop in plasma cholinesterase levels benefit greatly from neuromuscular monitoring [62, 99-103]. During this time, foetal monitoring should preferably be done using a Doppler ultrasound. Any type of emergency surgical surgery requires pre-, intra-, and post-operative foetal monitoring. Because of the problems generally associated with GA in this segment of the population, including difficult airways and a high risk of aspiration, regional anaesthetics should be the primary choice whenever possible [17]. During the first trimester, the danger of teratogenicity in the foetus is the highest, and all essential medicines should be delivered after a close discussion between the anaesthesiologist and the obstetrician.

8.2. SECOND TRIMESTER

To lessen the risk of spontaneous abortion and premature labor, it has been standard practice to postpone surgery until the second trimester. By this time, the majority of physiological changes have reached a plateau, making anaesthetic management safer than in the first or third trimesters. Although the second trimester is believed to be a safer phase for emergency surgery than the first and third trimesters, it is nevertheless connected with several substantial physiologic changes that can endanger both the mother's and the foetus' lives.

Airway management becomes even more difficult. The gravid uterus begins to compress the larger vessels, and aorto-caval compression can be quite dangerous when general or regional anaesthesia is administered. Acute appendicitis, cholecystitis, and intestinal blockage are the most common non-obstetrical surgical emergencies that complicate pregnancy. Torsion of ovarian cysts or masses, cholelithiasis, adrenal tumor, hernias, complications of inflammatory bowel disease, or stomach pain of uncertain aetiology are among the less common surgical diseases [3, 104].

A left lateral position or keeping a wedge under the right side while supine can help prevent aorto-caval compression. Due to the diminished capacity of the epidural space, venocaval compression causes distension of the epidural venous plexus, which raises the risk of inadvertent intravascular injection of local anaesthetics (LAs) as well as rapid distribution of the LA medication. During pregnancy, there is a significant increase in the levels of pro-coagulant factors, resulting in a hyper-coagulable state that begins in the late first trimester and reaches a plateau in the second trimester. These alterations necessitate thromboprophylaxis in high-risk patients who are more likely to have this problem after the second trimester [105].

8.3. THIRD TRIMESTER

In the third trimester, decision-making gets a little easier because a caesarean section can be performed before the major surgery. Due to increased airway oedema caused by hormone interactions, all additional challenges to airway control during the first two trimesters are amplified. An emergency operation after 28 weeks can be performed with the introduction of steroids, which give critical cover for foetal lung maturation and prevent the neonate from developing acute respiratory distress syndrome [99].

The precautions taken in the second trimester apply equally effectively in the third trimester, with a higher risk of aorto-caval compression due to a considerably larger gravid uterus than in the second trimester. Even during this time, regional anaesthetic is the recommended option due to the inherent danger of GA in parturients. GA should be used with caution because inhalational anaesthetics can cause significant uterine relaxation, which can lead to post-partum bleeding [106, 107]. For caesarean birth, analgesics, sedatives, and anaesthetics must be used with prudence because they can have a significant impact on infant health and Apgar scores. Several medicines, as well as surgical and anaesthetic stress, have the potential to suppress lactation, which may or may not be temporary, necessitating particular caution during anaesthesia. One major source of concern during this time is the likely emission of various medicines through breast milk, which might have negative effects on the newborn during nursing, particularly opioids and sedatives.

9.1. LABOUR ANALGESIA

Since its origin, both in industrialized and developing countries, labor analgesia has been connected with misconceptions and disputes. Since the early 1950s, when labor analgesia was first introduced into clinical practice, obstetrical anaesthetic science has changed dramatically because of the development of sophisticated procedures, monitoring devices, and the availability of newer, safer, and more effective medicines [108]. As a result, over the last two decades, the quality of labor analgesia methodology has vastly increased. The development of obstetrical anaesthesia as a subspecialty has aided the growth and advancement of labor analgesia science [109]. Although non-pharmacological treatments like water baths, intradermal sterile water injection, TENS, hypnosis, and acupuncture are still used in some parts of the world, pharmacological methods have been the cornerstone in the provision and advancement of labor analgesia [110].

Pethidine, fentanyl, tramadol, butorphanol, and remifentanil are examples of parenteral opioids that have been successfully utilized for labor analgesia, but no one agent is without adverse effects when given in greater dosages [111-114]. Inhalational medicines such as Entonox and the short-acting fluorine anaesthetic sevoflurane are less effective, but they are not without adverse effects, especially at higher doses [115, 116]. The breakthroughs in regional anaesthetic technology have taken labor analgesia to new heights. The use of lower doses of LAs and opioids in epidural and combination spinal epidural analgesia has proved revolutionary in reaching the intended goals of labor analgesia [117]. The modern methods of the drug delivery system, such as continuous epidural infusion using infusion pumps, patient-controlled analgesia, and computer-integrated, patient-controlled epidural analgesia, have mostly been essential in popularizing the science of painless labor [118-120]. The introduction of newer LAs such as levo, bupivacaine and ropivacaine has improved the safety of labor analgesia even further [121]. Adjuvants such as opioids, α-2 agonists such as clonidine and dexmedetomidine, neostigmine, and others enable not only the necessary analgesia to be achieved with lower dosages of LA but also the analgesic effect to be prolonged [122-125]. Overall, lower LA dosages have almost eliminated the different side effects associated with greater concentrations of the anesthetic drugs, making labor virtually painless. Although some studies indicate that pain-relieving interventions during labor are linked to a higher rate of operational delivery, there is no considerable literature to back up these claims [126].

9.2. ANAESTHESIA FOR OPERATIVE DELIVERY

A recent trend has shown an increase in the frequency of caesarean sections performed for one reason or another in both developed and developing countries [127-129]. Advanced and timely foetal monitoring, which diagnoses early foetal compromise and increases patient preference for operative delivery, are two more possible causes for these surgical treatments [106]. Now that it has been proven that regional anaesthesia is far safer than general anaesthesia for caesarean sections, the majority of operational operations for delivery are performed under regional anaesthesia around the world [130]. The type of anesthetic used is heavily influenced by maternal preferences, concomitant conditions, and the urgency of the surgery [131-133].

Whatever the form of anesthetic is used, the most important element is the reduced frequency of maternal deaths as a result of enhanced anaesthetic care, especially in developed countries [134]. GA is used in a variety of situations [135], including

• Patient's refusal of regional anaesthesia
• Coagulation abnormalities
• Various contraindications to regional anaesthesia, such as severe active infection in the back, neurological diseases, spinal deformities, and so on
• Foetal compromise requiring immediate operative intervention

The most difficult component of providing GA to an obstetric patient is managing a difficult airway [136]. The anatomic and physiologic changes that occur during pregnancy, such as soft tissue oedema of the upper airway, weight gain, breast enlargement, increased mucosal vascularity with an increased propensity to bleed, and a high risk of aspiration pneumonitis, make airway management extremely difficult [100]. Because the hormonal imbalance lowers the tone of the upper esophageal sphincter, even with sufficient fasting, there is always a danger of aspiration in these patients. Due to the prolonged gastric emptying time and intra-abdominal pressure caused by a gravid uterus, the risk of pulmonary aspiration is increased even more [137]. In such patients, quick sequence induction and intubation is the preferred approach to securing the airway, and a variety of anaesthetic methods are available to reduce the stress reaction associated with airway manipulation and intubation [138]. Newer supraglottic devices, such as the proseal laryngeal mask airway and the intubating laryngeal mask airway, have made administering GA and managing a difficult airway even easier [136, 139].

Not only is regional anaesthesia connected with the avoidance of airway manipulation, but it also has the advantage of avoiding the polypharmacy used in general anaesthetics. Regional anaesthetic also allows the parturient to stay awake during the surgical procedure and hear the baby's first cry, which can provide a psychological boost to nervous patients [106, 140]. Although both spinal and epidural techniques have proven to be effective, spinal anaesthesia is more common and important when a quick delivery is required, and the cost-effectiveness of spinal anaesthesia is more comforting to the patient's relatives than epidural, particularly in developing countries [130, 141]. The epidural is a more versatile approach because it can be utilized for labor analgesia and operational interventions using the same catheter if necessary. Many parturients prefer this procedure since it allows them to have a longer period of pain-free recovery. If the sensory level exhibits early regression during the surgical operation, this approach has the added benefit of extending the block height. Increased costs and a longer time to achieve a sufficient block are only a few of its major drawbacks [142]. Sensory anaesthesia is established in a significantly shorter time with the inclusion of adjuvants such as opioids and α-2 agonists and with a lower dose of Lasix (furosemide) [125]. The benefits of both spinal and epidural anaesthesia are combined in the combination of spinal epidural anaesthesia. It not only creates a quick and dense block but also a pain-free postoperative time with top-up dosages. The applicability of this methodology is particularly important in high-risk patients, such as those with heart disease, diabetes, or pre-eclampsia [143]. Although many anaesthesiologists favor GA for eclampsia patients, in problematic cases, a graded epidural approach with titration of the local anaesthetic dose is equally effective. Given the disordered pathophysiology in pre-eclampsia patients, achieving stable haemodynamics is critical [144].

9.3. ANAESTHESIA FOR POST-PARTUM PERIOD

The postpartum period begins after the placenta is delivered and can last up to 6 weeks. Surgical procedures should be avoided as much as possible during the first six weeks after delivery. During these 6 weeks, normal physiological parameters are being restored to prepregnancy levels, and as a result, anaesthetic responses can be unpredictable or exaggerated. The most prevalent emergency in the immediate postpartum period is a high risk of postpartum haemorrhage, which necessitates the use of an anaesthesiologist during the surgical intervention [145]. Furthermore, many tubal ligation procedures are performed around this time in underdeveloped countries like India to guarantee maximal patient cooperation for family planning aims. In the background of these alterations, the physiological changes match the early portion of the first trimester and have anaesthetic implications that are practically identical. Because only the mother body has to bear the burden of any procedure, the risk is often lessened. There is still a potential that medicines supplied as part of the therapy regimen will get into breast milk. Anatomical changes are noticeable after childbirth, which greatly aids tubal ligation. The abrupt rise in blood volume owing to auto-transfusion after birth, which can cause congestive heart failure, is the most important factor in patients with cardiac illness during this time. Because rapid infusion can cause a substantial lowering of systemic vascular resistance and increase of pulmonary vascular resistance, which leads to decreased cardiac output, the rate of oxytocin infusion must be controlled and should be given at 60-80 mIU/min. Methylergometrine and PGF2-α can produce significant hypertension, tachycardia, and increased pulmonary vascular resistance in cardiac patients, which can be highly dangerous.

10.5.1. Regional Anesthesia

Spinal or epidural anesthesia can be given safely if the patient is conscious, seizure free, with stable vital signs, and with no signs of raised ICP. Moodley et al. [157] found no difference in maternal and neonatal outcomes when comparing epidural versus general anesthesia for cesarean section in conscious women with eclampsia. Spinal anesthesia with low-dose bupivacaine with fentanyl is a good option. Safety of spinal anesthesia has been studied in eclamptic by Razzaque et al. [158], who concluded that spinal is safer than GA for LSCS in eclamptic. A prospective cohort comparison by Antonie et al. [159] in patients with severe pre-eclampsia concluded that pre-eclamptic patients experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients. Hyperbaric bupivacaine (7.5 mg) with 25 μg fentanyl provides adequate anesthesia for cesarean section. If a CSE technique is instituted, the presence of the epidural catheter provides the flexibility to extend the level and the duration of the block. Contraindications to regional anesthesia include patient refusal, DIC, and placental abruption. Regarding administering spinal anesthesia in patients on aspirin, it has been recommended by the American Society of Regional Anesthesia that low dose aspirin therapy is not a contraindication to regional technique [54]. Regional anesthesia is considered safe when the platelet count is more than 75 000 per micro liter. A platelet count of more than 50,000 per micro liter is generally considered a contraindication. Within the range of 50-75 thousand per micro liter, an individual assessment (considering patient risk and coagulation tests) is necessary. The anesthesiologist should also maintain vigilance on the pulmonary function, urinary output, evidence of aortocaval compression, and epidural-induced systemic hypotension that may lead to decreased uteroplacental blood flow. Small incremental intravenous doses (50 ug) of phenylephrine may be used to treat hypotension temporarily while additional intravenous fluid is infused judiciously.

10.5.2. General Anesthesia

General anesthesia (GA) is the choice in the unconscious, obtunded patients with evidence of increased ICP. Anesthesia is achieved with an opioid and relaxant technique and deliberate hyperventilation [151]. The important considerations are

• Airway edema
• Possibility of difficult airway management
• Although cholinesterase levels decrease, the duration of action of succinylcholine and ester local anesthetics is seldom affected
• Exaggerated hypertensive responses to endotracheal intubation
• Drug interaction between magnesium and muscle relaxants
• A small dose of a volatile halogenated agent may prevent awareness
• Extubation is done in the left lateral position when the patient is fully conscious or else the patient is transferred to ICU for ventilatory support, depending on the preoperative condition and intraoperative behavior.

Initial finding seen in most cases is low CVP and high left-sided filling pressure (PCWP). If urine output is adequate, there is no necessity for any special monitoring. If urine output is not adequate, a fluid challenge is done with 250-500 ml of crystalloid infused over 20 min. If a response is seen, additional fluid boluses may be given cautiously. If there is no response to the initial fluid, bolus, CVP or PCWP, monitoring becomes necessary. Pulmonary artery catheter is indicated in severe pulmonary edema, oliguria unresponsive to fluid therapy, and intractable hypertension [160].

Currently, a volume expansion to CVP of at least 6-8 mmHg is considered safe and effective. Young et al. [161], in their study on hemodynamic, invasive, and echocardiographic monitoring in hypertensive parturients, found that the CVP-PCWP gradients in severe preeclampsia may be as high as 8-10 mmHg. Therefore, a CVP of 8 mmHg might correspond to a PCWP as high as 18 mmHg. This results in volume overload and possibly pulmonary edema. Hence, the aim of volume expansion to achieve a CVP of 4 mmHg or less may be better in eclamptic.

Even though individual cases differ, invasive blood pressure monitoring is required in the following situations [162].

• Sustained high BP
• Potential rapid BP fluctuations
• Inability to obtain BP by cuff
• Repeated sampling
• Use of peripheral vasodilators
• Concepts about pulmonary edema.

Pulmonary edema is a dangerous complication that may be either cardiogenic or noncardiogenic [163]. Cardiogenic pulmonary edema is due to either impaired left ventricular systolic or diastolic function. The presence of low CO, high PCWP, high CVP, and high SVR characterizes systolic dysfunction, whereas diastolic dysfunction is associated with normal or high CO, high PCWP, and normal SVR. Noncardiogenic pulmonary edema results from such factors as increased capillary permeability, iatrogenic fluid overload, an imbalance between colloid osmotic pressure (COP) and hydrostatic pressure, or a combination of these factors. The management varies according to the cause and clinical dysfunction.

In severe preeclampsia, vasospasm and endothelial dysfunction lead to a reduction in GFR. Rising serum creatinine and oliguria signal rapid deterioration of renal function. Clark et al., in their study on managing hemodynamic subsets of oliguria in preeclampsia, described three distinct types of hemodynamic findings [164]. The first group showed classic signs of hypovolemia as evidenced by low filling pressures, elevated SVR, and hyperdynamic cardiac function. These responded well to IV fluids. The second group showed normal or elevated filling pressures, elevated CO, and a high SVR. These patients were treated with vasodilators and fluid restriction. The third group showed elevated SVR and PCWP, and depressed cardiac function responded well to after-load reduction. So treatment for oliguria is situation based.

Women with pre-eclampsia are at increased risk of thromboembolic disease. Before delivery, all patients should have antiembolic stockings or low molecular weight heparin while immobile. Following delivery, low molecular weight heparin (dose adjusted on early pregnancy weight) should be given daily until the patient is fully mobile (seven days if delivered by Caesarean section). Low molecular weight heparin should not be given until 4-6 h after spinal anesthesia. An epidural catheter should be left in place for at least 12 h after low molecular weight heparin administration. Following removal of an epidural catheter, low molecular weight heparin should not be given for 4-6 h [54].