Pregnancy with co-morbidities: Anesthetic aspects during operative intervention

Abstract

The presence of co-morbidities during pregnancy can pose numerous challenges to the attending anesthesiologists during operative deliveries or during the provision of labor analgesia services. The presence of cardiac diseases, endocrinological disorders, respiratory diseases, renal pathologies, hepatic dysfunction, anemia, neurological and musculoskeletal disorders, connective tissue diseases and many others not only influence the obstetric outcome, but can significantly impact the anesthetic technique. The choice of anesthesia during the pregnancy depends upon the type of surgery, the period of gestation, the site of surgery, general condition of patient and so on. Whatever, the anesthetic technique is chosen the methodology should be based on evidentially supported literature and the clinical judgment of the attending anesthesiologist. The list of co-morbid diseases is unending. However, the present review describes the common co-morbidities encountered during pregnancy and their anesthetic management during operative deliveries.

INTRODUCTION

Pregnancy is a state, which exhibits wide alteration of normal physiological parameters. In the background of these physiological changes, the pre-existence or development of co-morbidities during pregnancy can impact the obstetrical outcome. The presence of cardiac diseases, endocrinological disorders, respiratory diseases, renal pathologies, hepatic dysfunction, anemia, neurological and musculoskeletal disorders, connective tissue diseases and many others not only influence the obstetric outcome, but can significantly impact the anesthetic technique and pose numerous challenges to the attending anesthesiologists.[1] Reports of confidential enquiries into maternal deaths have clearly shown the significant role of anesthesia in decreasing the maternal morbidity and mortality. The present review is written with an emphasis on common co-morbidities encountered during pregnancy and their anesthetic management during operative deliveries. The search strategies for the manuscript included search for full text articles and ongoing clinical studies related to various medical diseases during pregnancy. The literature search was carried out from PubMed, PubMed central, science direct, Scopus, Wolters Kluwer, Medscape and Google.com. The key words for search included, but were not limited to anesthesia in pregnancy, medical diseases during pregnancy, hematological disorders, anemia, asthma, cardiac diseases, critically illness during pregnancy, endocrine disorders of pregnancy, diabetes during pregnancy and so on.

MEDICAL DISEASES AFFECTING ANAESTHETIC MANAGEMENT DURING PREGNANCY

Anesthesia in pregnant cardiac patients

These parturients are the most challenging to the anesthesiologists as cardiac diseases present in numerous pathological forms with a variable severity. The anesthesiologist requires a complete knowledge of the type, severity and prognosis of cardiac diseases such as mitral stenosis, mitral regurgitation, aortic stenosis, aortic regurgitation, congenital heart diseases (left (L) to right (R) and R to L shunts), primary pulmonary hypertension (HTN), hypertensive disorders, cardiomyopathies, coronary artery disease (CAD) and various rhythm disturbances.[2,3,4,5,6] The anesthetic technique, general or regional, is best determined by certain factors such as the threshold of the parturient to the pain of labor and surgery, response of the parturient to the clinical effects of the oxytocics, methylergometrine, prostaglandins, hemorrhage, post-delivery physiological responses to sudden relief of venocaval obstruction and auto-transfusion of blood from uterine contractions. Any ongoing cardiac medication should be given as usual to provide clinical cover for prevention of any cardiac complication.[7,8,9]

Rheumatic heart disease (RHD) is still the most common of the heart ailments especially in the developing nations like India where it accounts for almost more than 80% of the heart ailments during pregnancy.[10] The higher mortality and morbidity in these patients is mainly associated with mitral stenosis, which is the most common complication of RHD.[11] The main anesthetic goals during the management of patients with mitral stenosis include:

1. Maintenance of heart rate on the slower side

2. Avoidance of pain, hypoxia and hypercarbia

3. Prevention of aortocaval compression

4. Prevention of atrial fibrillation and its immediate management

5. Maintenance of cardiac output and adequate venous return.

The preferred technique in such patients is “graded epidural” anesthesia whereby one can easily titrate the dose of local anesthetic and prevent the occurrence of any instability in the hemodynamic parameters and its associated adverse consequences. Moreover, the gradual segmental block achieved with titrated anesthesia spares the peripheral pump due to gradual sympathetic blockade and helps in achieving adequate venous return.[12] The cardiac disease during pregnancy can be further classified according to the severity of its pathophysiology and risk [Table 1] to the parturient.

Table 1.

Cardiac diseases complicating pregnancy with their risk profile

Anesthetic management in parturients with endocrine disorders

One of the most challenging aspects in diabetic parturient involves the adequate control of blood sugar so as to prevent the occurrence of neonatal hypoglycemia.[13,14] There exists a high association of diabetes mellitus (DM) with other co-morbid diseases such as HTN, CAD, pre-eclampsia, renal dysfunction, autonomic neuropathy and so many others. The presence of autonomic neuropathy makes a diabetic parturient highly vulnerable to hemodynamic instability.[15] General anesthesia (GA) is more hazardous in these patients due to high probability of difficult airway management due to limited atlanto-occipital joint extension, exaggerated and unpredictable response to stress during intubation and impaired counter regulatory responses to fluctuating blood sugar levels.[16] Management of diabetes is challenging as the requirement of insulin increases two-fold near term gestation. As such, perioperative status has to be optimized with appropriate insulin regimen taking care not to induce hypoglycemia with aggressive control of hyperglycemia.[17]

Regional anesthesia is much safer than GA as responses to hypoglycemia are blunted in these patients and are difficult to diagnose under GA whereas during rheumatoid arthritis (RA) patient will be able to convey the things verbally. The drawback in DM patients with autonomic neuropathy receiving RA includes exaggerated sympathetic response due to autonomic imbalance.[15,18,19] Therefore, monitoring should be intense and vigil in patients with co-morbid pathologies and ideally all these cases should be taken up in a tertiary care centers with intensive care unit (ICU) back-up facilities especially in developing nations.

Thyrotoxicosis is another common endocrine disorder, which needs special attention during operative or vaginal delivery besides a good control during the antenatal period. A thorough evaluation of cardiac status is mandatory during the pre-anesthetic examination so as to exclude any arrhythmias or sign of cardiac disease, which can increase the morbidity and mortality.[20] Other endocrine disorders though rare, but nevertheless demand an extreme vigil during operative delivery.

Anesthetic management in asthma and respiratory diseases

The incidence of pregnancy-induced hypertension (PIH), prematurity, antepartum and postpartum hemorrhage, low birth weight, neonatal hypoxia and perinatal mortality are much higher in patients with asthma as compared with normal pregnant patients. All the potential complications either results from the disease process or develop as a part of complications associated with the various therapeutic regimens.[21,22] GA is very hazardous in this subset of population due to exaggerated airway responses due to inherent bronchial smooth muscle hypersensitivity and narrowing of the airways due to inflammatory process.[23] The use of corticosteroids particularly is associated with a higher incidence of PIH. Poor control of asthma is associated with a higher incidence of adverse outcome. Therefore, aggressive management of asthma is mandatory during the pregnancy so as to decrease the maternal and perinatal mortality.[24]

Other respiratory diseases may exhibit an obstructive (cystic fibrosis, tuberculosis, bronchiectasis) or restrictive pattern (fibrosing alveolitis, sarcoidosis, fibrosis) which can impact the morbidity and mortality during operative delivery.[17] Though regional anesthesia is preferred, GA may be required in few emergency situations, which can enhance the morbidity statistics. The availability of pulmonary function tests is of extreme help to the anesthesiologists and such deliveries should be undertaken in the institutions.[17,25]

Parturients with neurological, neuromuscular and musculoskeletal disorders

Neurological diseases (seizure disorders, multiple sclerosis spina bifida, hemiplegic migraine, any infective infection, trauma, tumors) neuromuscular disorders (myasthenia gravis, poliomyelitis) and musculoskeletal disorders (scoliosis, kyphoscoliosis) can influence the obstetric outcome during operative deliveries as the involvement of nervous and musculoskeletal system can be highly variable.[17,26,27] Ideally all such operative interventions should be referred to tertiary care centers with availability of obstetricians, neurosurgeons, neurologists, radiologists and anesthesiologists. Cardio-respiratory evaluation should be thoroughly done as the anesthetic technique is directly impacted by degree of impairment in cardio-respiratory reserve. Planning of anesthesia is mandatory during pre-anesthetic stage with strategies to control any seizure activity during perioperative period. Regional anesthesia is preferred in the majority of patients with these disorders except for few strong contraindications such as increased intracranial pressures, tethered spinal cord and others. Patients who are at high risk of developing intra-operative respiratory insufficiency (kyphoscoliosis) should preferably be administered regional anesthesia in an incremental manner.[17,26,27] Myasthenia gravis should be adequately treated preoperatively with anticholinesterases and regional anesthesia is preferable if respiratory functions are not impaired.[28] Patients with multiple sclerosis should be administered succinylcholine cautiously and only if strongly indicated as they are at high risk of developing hyperkalemia and cardiac arrest due to up-regulation of nicotinic acetylcholine receptors.[29] The neuroprotection during perioperative period applies both for the general and regional anesthesia, but mannitol, dexamethasone and frusemide should be used judiciously as it can compromise uterine perfusion.[30] The parturients with mental illness and psychiatric disorders should be evaluated by a psychiatrist, obstetrician and anesthesiologist during the pre-operative evaluation for a better outcome as such patients are highly challenging to anaesthetize. Multidisciplinary team work, specific precautions and pre-anesthetic optimization can certainly contribute to an improved outcome in patients with neurological and muscular disorders during the peripartum period.

Renal diseases and anesthetic challenges

Patients suffering from renal diseases need a strict and vigil monitoring so as to achieve a better obstetrical outcome during pregnancy. The incidence of acute renal failure (ARF) in pregnancy is about 1/20,000 births with mortality varying from 10% to 56%.[31,32] 2-3% of renal diseases in pregnancy can be attributed to functional failure as electrolyte and water disturbance can occur due to hyper-emesis gravidarum, blood loss, diarrhea and so on.[33] The incidence of acute pyelonephritis is variable, but is approximately 40% in parturients with bacteriuria.[34] Renal obstruction and failure can result from nephrolithiasis and gravid uterus obstructing ureters.[35] Acute tubular necrosis (ATN) is a major cause of renal failure in developing nations, which can have numerous causes.[36] Treatment of pre-renal or functional ARF in pregnancy is to correct the underlying cause that is replete the lost volume or blood and treat sepsis. Progressive ARF ATN may be avoided with an excellent chance of complete recovery of kidney functions with timely therapeutic intervention by allowing immediate delivery and treating underlying renal disease with occasional support from hemodialysis and peritoneal dialysis. However, depletion in intravascular volume should be avoided.[37]

The challenges for the attending anesthesiologists rise significantly if patients have advanced renal disease.[38] Regional anesthesia is considered safe if coagulation parameters are normal.[39,40] Among GA, total intravenous anesthesia is considered better as inhalational anesthetics are primarily excreted through kidneys, which can enhance the incidence of renal toxicity and renal failure.[41] The dose of anesthetics and analgesics can be reduced by pre-operative administration of dexmedetomidine, which can enhance the safety of the anesthetics.[18]

Atracurium is preferred as it is not dependent upon hepatic or renal metabolism for its elimination while succinylcholine can cause fatal arrhythmias if any evidence of hyperkalemia is present. Opioids should be avoided as they accumulate during renal failure, however, newer and short acting opioids such as fentanyl and remifentanil can be used. Alprazolam and midazolam can be safely used as sedative agents as they are short acting benzodiazepines. The basic aim of anesthesia in the pregnant patient with renal disease is to protect the renal tissue besides achieving successful obstetric outcome.[42]

Hematological disorders during pregnancy

Hematological disorders can be a cause of significant morbidity and mortality during pregnancy as the incidence of thrombosis and thromboembolism can be significant in certain clinical situations. The higher levels of fibrinogen, factors VII, VIII and XIII, activation of platelets and fibrinolytic factors results in a state of hypercoagulability and increased incidences of thromboembolism. Routine screening for hematological disorders such as thalassemia, sickle cell disease and anemia has resulted in lowering the mortality especially in developing nations.[17] The routine use of thromboprophylaxis in such patients can result in a significant reduction of morbidity and mortality during operative deliveries. There are concerns of spinal hematoma in patients receiving anti-coagulants during neuraxial anesthesia for operative deliveries. The newer guidelines have been published, which have clearly stated about the safe practice of neuraxial anesthesia in patients receiving low-molecular weight heparin.[43,44] Newer orally active anti-coagulants have become available, which have also been approved by Food and Drug Administration (FDA), but their usage in pregnancy is still under review.[45] However, the administration of neuraxial anesthesia in parturients receiving anti-coagulant drugs should be individualized and a thorough risk-benefit analysis is essential depending upon the urgency of obstetric surgery. The anesthesiologist needs to be aware of the various pharmacokinetics and pharmacodynamic properties of these drugs so as to decide anesthetic technique within the limits of the available guidelines.

Liver disease and pregnancy

Pregnancy with liver disorders can influence anesthetic technique and type of various anesthetic and analgesic drugs used during operative deliveries. Intra-hepatic cholestasis of pregnancy, hepatitis, cholelithiasis, HELLP syndrome (hemolysis elevated liver enzymes low platelets counts), acute fatty liver of pregnancy, hepatic rupture and infarction, hyper-emesis gravidarum and other liver pathologies can be highly challenging to the attending anesthesiologist due to deranged liver functions and drug metabolism.[46,47,48] Reduced synthesis of plasma protein can increase the unbound fraction of drugs such as thiopentone sodium and as such doses should be reduced. Dose of propofol also needs reduction as the higher doses can cause cardio-respiratory depression and increased sedation. Increased volume of distribution and altered protein binding causes a relative resistance to the action of non-depolarizing muscle relaxants. Reduced hepatic blood flow and extraction ratio can impact the clearance of opioids, thus enhancing their action and side-effects. Apart from desflurane, all other volatile chlorinated agents reduce hepatic blood flow and can exaggerate the hepatic dysfunction.[49] Other serious concerns are related to active viral infections with hepatitis B and C viruses, which besides causing liver dysfunction are potentially dangerous to anesthesia providers.[50] Preoperatively, mandatory investigations should include liver functions tests including coagulation profile, intra-vascular volume status and neurological assessment besides screening for the viral markers. Blood and component therapy should be available in hand before taking any major surgical procedure. Invasive monitoring should be performed only in those cases where it is mandatory and should be avoided routinely.

Connective tissue disorders

Connective tissue disorders pose unique challenges to the attending anesthesiologist during the peri-op period in pregnant patients. RAs, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, polyarteritis nodosa, dermatomyositis, polymyositis, wegener's granulomatosis, sarcoidosis and many others require careful pre-anesthetic evaluation so as to design a suitable anesthetic technique and plan on an individual basis depending upon the severity of the disease and the current therapeutic regimen being administered.[17,51,52,53,54,55] Flexion abnormality and involvement of cricoarytenoid joint may pose difficult airway problem in patients with RAs. Cardio-respiratory monitoring is essential during the post-operative period as well these patients are likely to develop respiratory insufficiency. Such patients should ideally be shifted to ICU. Major limitation of ankylosing spondylitis is the immobility of the cervical spine, which can pose intubation problems. Fiber-optic bronchoscopy aided intubation should always be ready in such cases. Renal involvement in systemic lupus erythematosus mandates administration of those anesthetic drugs, which are not dependent upon renal excretion. Multisystem involvement in scleroderma can pose challenges during airway management, risk of aspiration, difficulty in securing intravenous access, cardiac manifestations and progression of renal disease and difficulty in monitoring. Peripharyngeal edema, HTN and thrombosis of coronary and cerebral vessels can pose unique challenges to the attending anesthesiologists.[17,51,52,53,54,55] Anesthetic issues are related to multiple muscle inflammation, dermatitis and edema in patients with dermatomyositis/polymyositis. Though Wegener's granulomatosis is characterized by multisystem involvement, renal disease is of particular concern during anesthesia administration. Similarly, pulmonary and cardiac tissue pathology is of serious concern during administration of anesthesia in patients with sarcoidosis while metabolic, hypercalcaemia and hyperglobulinemia are also not of lesser concern in such patients.[17,51,52,53,54,55]

Anesthetic management of obese parturient

There are numerous anatomical, physiological and metabolic alterations in obese parturients, which produces a very challenging task for the attending anesthesiologist. The obese parturient invariably has a higher incidence of associated co-morbidities such as cardiac diseases, DM, obstructive sleep apnea, hepatic insufficiency, gallstone disease, etc., which makes them prone to develop various complications during anesthetic management.[56,57,58] GA is also associated with a higher incidence of perioperative mortality and morbidity. The major goals during anesthetic management of obese parturient[59,60] include, but are not limited to:

1. Titration of anesthetic drugs (especially opioids and sedatives)

2. Aspiration prophylaxis

3. Difficult airway management

4. Maintenance of stable hemodynamics.

As far as possible, patient should be positioned cautiously and should be made comfortable on the operation table by use of either a large size specially made tables or joining together of two operation tables. For any abdomino-thoracic surgery, post-operative analgesia should be adequate to prevent any obstruction or limitation of breathing movements due to pain. Though sometimes, it is difficult to administer regional anesthesia, but it should be a preferred choice in all such patients wherever possible.[61]

Anesthetic management of anemic parturients

South Asian countries account for almost 60-65% of the world's total anemic parturients and more than 50% of the total maternal deaths. The higher prevalence in these regions is most probably due to poverty, illiteracy, malnutrition, lack of health awareness, socio-cultural factors and poorly implemented health policies.[62,63] Hemoglobin value of lower than 11 g/dl or one-third fall in hematocrit is universally accepted as the quantitative parameter to define anemia, but its further classification is based on the numerical deficiency into mild (10-10.9 g/dl), moderate (7-9.9 g/dl) and severe (<7 g/dl) anemia. Though there are numerous causes of anemia in pregnancy, but the most common causes are iron, folate and vitamin B12 deficiency especially in the developing nations.[64]

The main pathophysiological alterations of anemia causes imbalance of oxygen carrying capacity and oxygen delivery to the tissues. As a result of severe anemia, various compensatory mechanisms in the parturient gets activated which causes a further increase in cardiac output, rightward shift of oxygen dissociation curve, increase in 2,3-diphosphate glycerate level, which further shifts the oxygen dissociation curve to the right, decrease in blood viscosity, increased stimulation of renal issue due to relative hypoxia leading to erythropoietin release.[65] In cases of severe anemia, the compensatory mechanisms can get blunted leading to the development of the right heart failure, coronary circulation compromise and tissue acidosis.[66] The anesthetic technique in parturients with severe anemia depends upon a multitude of factors such as severity of anemia, co-morbid diseases, type of surgery and anticipated hemorrhagic loss. The main anesthetic goals during these surgical interventions include:

1. Avoidance of hypoxemia and adequate oxygenation

2. Minimal time in securing definitive airway during GA

3. Maintenance of stable hemodynamics

4. Avoidance of hypothermia

5. Avoidance of hyperventilation.

As far as possible, regional anesthesia should be the preferred choice wherever feasible as it is associated with decreased blood loss and adequate analgesia. It is always advisable to use vasoconstrictors during surgery to maintain stable blood pressure.[66]

Management of critically ill obstetric patients

The role of anesthesiologist and the intensivist is equally challenging in such critically ill patients as they have a grossly deranged pathophysiology. The role of anesthesiologist is very vital in these situations as the majority of the ICU's throughout the world are being managed by the anesthesiologist. In developed countries like United States, only 0.2-0.9% of obstetric patients is admitted in critical care units. The availability of well-equipped modern labor rooms, excellent delivery services and specialized obstetric units are responsible for such a smaller number of obstetric admissions to ICUs. The approximate data depicts that only about 40,000-120,000 women in US require critical care services in proportion to 4.3 million births per year.[38,67,68] The exact similar data for developing nations is very difficult to obtain, but it reflects a very dismal picture as the maternal mortality rates are quite high in most of the Asian and African countries. Obstetric patients requiring intensive care can have complicated clinical course as compared to non-pregnant patients during various surgical and medical emergencies.[69,70] Factors such as hypoxemia, hypotension, severe infection, severe anemia, etc., can influence the obstetric outcome as both the parturient and fetus becomes extremely vulnerable to these clinical insults. The diseases, both specific and non-specific to pregnancy, affects equally in terms of increasing the morbidity and mortality in obstetric patients.[71,72,73,74] The respiratory diseases such as acute exacerbation of asthma, pneumonitis, pulmonary edema, acute respiratory distress syndrome and acute lung injury can have serious implications both for the mother and the fetus and special considerations during these episodes include maintaining oxygen saturation greater than 90%.[75] Cardiovascular diseases, such as RHD, mitral stenosis and other valvular lesions can cause cardiac failure, which necessitates intensive care admission. The cardiac surgery during pregnancy is extremely challenging and should best be avoided unless a lifesaving procedure is required. Renal diseases like pyelonephritis can be accentuated in the presence of sepsis, which again propels patient to the ICU. Coagulation disorders, hepatic derangements including HELLP syndrome warrants urgent intensive care intervention in many instances as these disease entities can prove fatal sometimes.[76,77] The neurological disorders can mimic the picture of eclampsia and appropriate therapy involves a complete investigation profile. Gestational diabetes, thyroid disorders and other endocrinal diseases can also be responsible for medical emergencies in obstetric patients requiring urgent critical care. Surgical emergencies though occur with equal frequency in both obstetric and non-obstetric population, require urgent attention especially in the critically ill obstetric patients. The decision to perform surgery again have to be taken after evaluating the pros and cons of surgical procedure as the critically ill-patients may not be able to sustain the anesthetic and surgical insults and fetal compromise is most likely to occur as well during these circumstances.[69,70]

Provision of quality intensive care requires acquisition of special procedural skills and thorough up to date knowledge of pathophysiological aspects of various clinical disease entities. Obstetrician's involvement is of prime importance when managing such cases in ICU irrespective of whether it is a closed or an open ICU. Their supervision and co-operation can decrease the maternal mortality and morbidity to a large extent. The outcomes are always best whenever a multidisciplinary approach is adopted in managing critically ill obstetric patients.[78]

Laparoscopic surgery during pregnancy

In developed countries, even laparoscopic procedures during pregnancy are also on the rise and few of them pertain to fetal surgery in utero. Pregnancy is no longer considered a contraindication for laparoscopic procedures and it has added advantages, which include shorter hospital stay, decreased post-operative pain, minimal exposure of fetus to the anesthetic agents, smaller and cosmetically sound skin incision and rapid recovery.[79] Whatever procedure is carried out during this period, universal precautions remains the same and it requires a good team effort from all quarters, especially the anesthesiologist and the obstetrician, to provide a safe atmosphere for both the mother and the fetus.

CONCLUSION

Co-morbidities during pregnancy can be treated and managed simultaneously by thorough pre-anesthetic evaluation and careful planning of anesthetic technique on individual basis. The choice of anesthesia during the pregnancy depends upon the type of surgery, the period of gestation, the site of surgery, general condition of the patient and so on. However, as far as possible, regional anesthesia should be the preferred technique whenever possible as it can have minimal effects on the maternal and fetal physiology as well as avoid the need for difficult airway management. Among the regional anesthetic techniques, epidural anesthesia is highly preferable as it not only serves the purpose of anesthesia, but will also provide a prolonged post-operative pain free period. The stable hemodynamic achieved is an added advantage of graded epidural analgesia. Labor analgesia with neuraxial technique has been made possible only with the advent of epidural anesthesia. Besides providing pain relief during labor, the flexibility of this technique allows for an operative intervention at any time through the same epidural catheter if spontaneous vaginal delivery fails. The choice of vasopressors to treat any hypotensive episode remains controversial as both ephedrine and phenylephrine have been used with equal success, but the main objective remains the same and that is to maintain a normal blood pressure rather than worrying about the vasopressor used.