|Year : 2021 | Volume
| Issue : 2 | Page : 70-80
Sickle cell disease in pregnancy and anaesthetic implications: A narrative review
Yudhyavir Singh1, Alka Chabra2, Vineeta Venkateswaran1, Anjan Trikha1
1 Anaesthesiology, Critical Care and Pain Medicine, AIIMS, New Delhi, India
2 Department of Anesthesia and Critical Care, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India
|Date of Submission||28-Aug-2021|
|Date of Acceptance||02-Sep-2021|
|Date of Web Publication||01-Oct-2021|
Dr. Yudhyavir Singh
Anaesthesiology, Critical Care and Pain Medicine, AIIMS, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Sickle cell disorder (SCD) is a genetic disorder of haemoglobin with a wide spectrum of severity and manifestations. It is a significant global public health problem and is mainly widespread among many tribal populations. Sickle cell disease (SCD) in pregnancy poses a unique challenge due to the physiological changes in pregnancy, the multitude of various organs involved, and its complications. The databases of PubMed, MedLine ResearchGate, EMbase, Scopus and Google Scholar were searched for literature about SCDs published up to 2021. Search terms and phrases used were 'sickle cell disease', 'sickle cell disease and pregnancy', 'anaesthesia and analgesia in sickle cell disease' and 'transfusion in sickle cell disease'. Original articles, guidelines, review articles, case reports, letters to editor and abstracts were reviewed with particular focus on pathophysiology and anaesthetic implications of sickle cell anaemia with pregnancy. While ample literature is available on SCDs, there is a paucity of literature on SCDs with pregnancy. In this review, we have attempted to present the relevant literature in a comprehensible manner.
Keywords: Blood transfusion, labour analgesia, multimodal analgesia, pregnancy, sickle cell disease, vaso-occlusive crisis
|How to cite this article:|
Singh Y, Chabra A, Venkateswaran V, Trikha A. Sickle cell disease in pregnancy and anaesthetic implications: A narrative review. J Obstet Anaesth Crit Care 2021;11:70-80
|How to cite this URL:|
Singh Y, Chabra A, Venkateswaran V, Trikha A. Sickle cell disease in pregnancy and anaesthetic implications: A narrative review. J Obstet Anaesth Crit Care [serial online] 2021 [cited 2022 Jan 24];11:70-80. Available from: https://www.joacc.com/text.asp?2021/11/2/70/327413
| Introduction|| |
Sickle cell disorder (SCD) is one of the most common monogenic disorders of inherited haemoglobinopathies, first described in the early 20th century. Worldwide, the prevalence of sickle cell carriers ranges from 50 to 60% affecting millions of people particularly affecting Sub-Saharan Africa, South Asia and Mediterranean countries. Sickle haemoglobin was first described in the tribal population of South India by Lehman and Cutbush in 1952. In India, HbS is widely spread among the tribal populations of Southern, Central and Western states reaching as high as 48% in some communities. The disease continues to be widespread among many tribal people in India, with Madhya Pradesh and Maharashtra bearing the burden of the largest number of cases. SCD is a multiorgan and multisystem disorder and pregnancy with SCD has a reciprocal influence on each other and their association is detrimental as the physiological changes that occur during pregnancy can over burden various organs that have been already affected due to SCD with subsequent increase in maternal and foetal complications. Despite developments in the management of SCD over the past few decades, pregnancy complicated by this disease remains associated with adverse maternal and perinatal outcomes. This review provides an overview of the pathophysiology of SCDs in pregnancy and the anaesthesiologist perspective on the management of labour pain, caesarean delivery, and postoperative analgesia.
| Pathophysiology and Genetics|| |
SCD is an autosomal recessive disease arising due to single gene mutation (GAG-GTG and CTC-CAC) in chromosome 11, causing substitution of the nonpolar amino acid valine in place of the negatively charged glutamate in the sixth position of the β-chain of the haemoglobin molecule.,, Due to this, the 'normal adult haemoglobin A' is replaced with 'haemoglobin S'. Sickle cell disease (SCD) is a homozygous state and the most severe form caused by inheriting two copies of HbS, with HbS (α2/β2) accounting for 70-98% of the total haemoglobin (α2/βs2). Sickle cell trait (SCT) also known as a 'carrier state' is a heterozygous condition. The haemoglobin molecule is composed of normal α-chains and a combination of normal β-chains as well as β-chains carrying the sickle mutations (α2/βsβ, HbSA). Other forms include compound heterozygous conditions such as Hb D, HbC with HbS, HbS with β+ thalassemia.
In SCD, erythrocytes undergo rapid but reversible change in shape on deoxygenation (PaO2 <50 mmHg) and intracellular polymerization of abnormal HbS molecule stretches the normal flexible biconcave shape into elongated rigid form, and thus deforming the cell, imparting a 'sickle' shape to the cell, which gives the disease its name. The polymers disaggregate with oxygenation and restore normal shape. However, repeated sickling cycles and extensive polymerization of HbS produce erythrocyte metabolic abnormalities and membrane damages subsequently leading to irreversible sickling regardless of oxygen concentration and intravascular haemolysis of red cells. Sickle cells are rapidly cleared from the circulation by the reticuloendothelial system as a result of which the life span of erythrocytes is reduced to approximately 12 days. Damaged red cell membrane causes increased adherence to peripheral blood mononuclear cells, platelets and the vascular endothelium via P-selectin ligands present on the endothelial surface leading to vaso-occlusion, ischaemic-perfusion injury and end-organ damage. Release of free haeme and depletion of nitric oxide and arginine due to intravascular haemolysis worsen vascular endothelial injury leading to vasculopathy and its complications such as stroke, pulmonary hypertension, vaso-occlusion, acute painful crisis and end-organ damage [Figure 1]. It is suggested that microvascular occlusion occurs if the delay time (Td1) from deoxygenation of HbS to polymerization is shorter than the microvascular transit time (Tt). If the delay time is longer (Td2) or if the blood is flowing faster, the red cell transition to sickled shape takes place in a larger diameter postcapillary vessel, and thus occlusion is less likely to occur. Autonomic nervous system mediated vasoconstriction can decrease blood flow within seconds, thus increasing transit time, resulting in entrapment of sickle cell [Figure 2].
|Figure 1: Pathophysiology and mechanism of Vaso-occlusion in Sickle cell disease|
Click here to view
The diagnosis of SCD is simple and typically characterized by low haemoglobin, elevated reticulocyte count and presence of sickle cells in peripheral blood smear. Rapid sickle cell solubility test detects the presence of HbS and if positive, it is confirmed by techniques such as Electrophoresis, the most common technique using standard alkaline gel, isoelectric focusing or high-performance liquid chromatography [Table 1]. Prenatal screening is recommended in couples having a family history of SCD. In utero, amniocentesis or chorionic villus sampling obtains foetus cells to diagnose with restriction endonucleases. DNA-based or antibody-based tests are newer methods to offer an accurate point of care diagnostics.,
| Clinical Features of SCD|| |
SCDs clinically manifest as sickle cell disease (SCD), sickle cell trait (SCT) and sickle cell along other haemoglobinopathies. SCD presentations are severe, affecting all the body systems, whereas SCT is usually asymptomatic and has little or no clinical impact. Therefore, for this review, we shall be focusing on sickle cell disease (SCD).
Repeated cycles of haemolysis, inflammation and ischaemia relate to the acute and chronic clinical features of SCD [Table 2]. It is accompanied by intermittent periods of severe pain and complications with relative normalcy inbetween such episodes. Progression of SCD also varies widely, with some patients having an indolent course and others suffering from early organ damage and death, the latter usually due to pulmonary or neurological manifestations [Table 2]. The two most common SCD-related complication during pregnancy that requires prompt and well-structured delivery of emergent and specialized care are Vaso-occlusive Crisis (VOC) and Acute Chest Syndrome (ACS).
Vaso-occlusive crisis (VOC) in pregnancy
Vaso-occlusive crisis (VOC), also called 'painful crisis', is defined as an acute episode of pain in SCD not attributable to any other pathology. The presenting complaint is pain, primarily bone pain (due to bony infarction in the lumbar spine, femoral shaft or knee joint) or abdominal pain (due to infarction of the gastrointestinal tract, spleen, liver or referred pain from the rib). About 55% of parturients with SCD experience at least one episode of VOC during pregnancy. The incidence of VOC increasing with progression of pregnancy and peaking during the third trimester. Sometimes, the abdominal pain of VOC may mimic an acute abdomen requiring surgery but in pregnancy, the diagnosis is further complicated by the presence of a gravid uterus, which may potentially mimic labour pain. Therefore, it is of utmost importance to rule out other possible causes of pain to avoid unnecessary intervention. The parturient should be admitted to the hospital and treated immediately with analgesics, bed rest, adequate hydration and supplemental oxygen therapy, in case of desaturation. The present evidence suggests a multimodal approach with epidural analgesia as the mainstay of management, along with other modalities for pain management in VOC in these patients. Other supportive therapies such as anxiolytics and sedatives may be supplemented if needed. Transfusion therapy should be considered if there is severe anaemia with symptoms or VOC is complicated.
Acute chest syndrome in pregnancy
Acute chest syndrome (ACS) is an acute lung injury particular to SCD and is associated with significant mortality and morbidity. It is defined as the appearance of new pulmonary infiltrates involving at least one lung segment on chest radiography, along with chest pain, fever more than 38.50C, tachypnoea, wheezing or cough. It is mostly precipitated by infections, whereas other causes include fat embolism after bone marrow infarction or pulmonary infarction. Signs and symptoms of ACS in parturients are similar to that of other SCD patients. Thus, if a parturient with SCD complains of severe coughing and chest pain, one should rule out ACS. Treatment includes supplemental oxygen therapy, bronchodilators, adequate analgesia, appropriate antibiotics in case of infection, hydration and blood transfusion if needed. Corticosteroids and inhaled nitric oxide have been suggested for treatment, but the evidence is unclear, with conflicting reports on benefit.
| Medical Management of SCD|| |
Hydroxyurea as a potent ribonucleotide reductase inhibitor inhibits intracellular polymerization and enhances the production of HbF in sickle cell disease. Some of these patients may be on chronic hydroxyurea therapy, which is the only proven medication in SCD capable of reducing the overall incidence of VOC and ACS. However, it is potentially teratogenic. Although a large, multicentre trial by Ballas et al. over 17 years found no evidence of teratogenic changes in any of the pregnancies studied, it may be prudent to advise women to discontinue the drug at least 3 months before conception.,
Angiotensin converting enzyme inhibitors (ACE)/angiotensin receptor blockers (ARB)
In SCD, renal dysfunction is commonly seen and present with proteinuria and microalbuminuria. The above drugs are used routinely in patients with SCD with significant proteinuria, as these agents reduce proteinuria and microalbuminuria. But these drugs are not safe in pregnancy and should not be used in women who are trying to conceive.
New therapeutic agents are under clinical trials that target specific pathophysiological pathways such as interrupting vaso-occlusion by reducing cellular adhesion, inflammation, hypercoagulability and prevention of intracellular HbS polymerization through HbF induction or Hb stabilization, for example Crizanlizumab (SelG1), Rivipansel (GM1-1070), poloxamer188, Heparins and Sevuparin. Anti-platelet drugs like prasugrel and ticagrelor are still under investigation while Statins have shown some novel means to prevent vaso-occlusion.,,,
Nutritional Supplements: Omega-3 fatty acids purified from fish oil are tested for benefits as an antioxidant, antithrombotic and anti-inflammatory benefit. The clinical trials have used products with different purity and proportions of types and dosages of omega-3 fatty acids. Folic acid is widely used in SCD patients with the rationale that the increased erythropoiesis can cause folate deficiency.
Role of blood transfusion
Blood transfusion (BT) forms the mainstay of treatment in SCD. Approximately 90% of adult SCD patients would have received at least one red blood cell transfusion during their lifespan. The benefit of transfusion includes decrease in the percentage of HbS, increase in oxygen-carrying capacity, improved haemoglobin, suppression of sickle erythropoiesis and dilution of HbS thus, preventing the sickle cell crises. Simple or top-up transfusions by buffy coat poor HbS free-washed RBC are usually done to increase the overall number of normal red blood cells and for immediate benefit in severe anaemia, acute aplastic crisis and before or during surgery. Stroke and acute chest syndrome represent acute end-organ damage state that benefits from exchange transfusion (erythrocytapheresis). It aims to remove HbS <30% by replacing it with HbA with maintenance of baseline haematocrit.
Several studies comparing aggressive versus conservative BT regimens in the perioperative period demonstrated no benefit of BT in preventing SCD complications.,, However, Howard et al. reported a lower rate of complications with preoperative BT in low- and medium-risk surgeries. We suggest that the same principles that guide decision-making for BT for surgeries may be applied for parturient in labour or planned for caesarean delivery, that is, anticipated blood loss resulting in decreased oxygen-carrying capacity. Numerous studies have been performed to determine whether prophylactic BT improves maternal and foetal outcomes in the parturient with SCD, with contradictory findings.,,,
When planned, preoperative BT should be given up to 14 days before surgery, and if not, must be given at least 24 hours before to utilize the oxygen transport capacity of the transfused blood. It is worth remembering that multiple BTs carry risks including infections, iron overload, alloimmunizations, transfusion reactions, hyperhaemolysis, and so on, and may increase the need for hospitalization during pregnancy. Thus, the transfusion benefits must be balanced against the various risks and an individualized plan made based on baseline haematocrit, end organ pathology, anticipated blood loss and planned mode of delivery.,,
Transplantation and gene therapy
The only curative modality for patients with SCD is Stem cell transplant with matched sibling donors but it is limited to procedures in children with the severe disease without end-organ dysfunction through the use of myeloablative conditioning regimes, which are toxic. However, using reduced toxicity conditioning regimes allows successful transplantation in adults and effective in preventing future painful VOC and stroke. Gene therapy to cure SCD is under clinical investigation. Clinical trials are ongoing for genes encoding anti-sickling beta-globulins, and gene correction therapy for HbF induction is still in preclinical stages.,,
Impact of sickle cell disease on pregnancy and delivery
The physiological changes of pregnancy and delivery may exacerbate SCD; conversely, the presence of SCD can complicate the course of pregnancy. Efforts should be made to optimize the woman's underlying condition as far as possible before planning for pregnancy. General measures include maintaining good hydration during physical exercise or hot weather, and avoidance of alcohol. In addition, a thorough haematological and cardiological workup, folate supplementation to avoid anaemia and blood transfusion if severely anaemic, should be advised. The normal haematological changes of pregnancy in addition to the SCD related alterations in blood profile cause a 'double impact' on the body. These patients already have pre-existing anaemia, increased oxygen demand and circulatory overload. All these changes are exacerbated by the normal physiology of pregnancy. Further, the aortocaval compression and venous stasis of pregnancy may place stress on the heart and worsen the baseline clinical condition. Moreover, pregnancy is a hypercoagulable state; this will not only favor sickling, but also increase the risk of thromboembolic phenomena like deep venous thrombosis and cerebral venous thrombosis. During the peripartum period, factors that increase sickling in women with SCD such as dehydration, hyotension, hypothermia and acidosis should be avoided.
The course of pregnancy in these women is rarely uneventful. Camous et al. found that 76% of the parturient with SCD in their studied cohort developed at least one SCD-related complication, whereas 51% developed complications in the antepartum period and 25% had postnatal sickling complications including ACS, VOC and stroke. There is an increased incidence of life-threatening placenta previa and placenta abruption (14% and 22%) in SCD patients. Furthermore, pre-eclampsia in the SCD patient is difficult to diagnose because symptoms such as abdominal pain, hypertension, kidney dysfunction and congestive heart failure may be manifestations of SCD. Pregnancy aggravates the pre-existing anaemia in SCD women, leading to a higher incidence of severe anaemia and increased requirement of blood transfusions.
These changes can also impact the mode of delivery and neonatal health. Parturient with SCD have been found to have a high rate of caesarean deliveries, ranging from 32% to 79%.,, In addition, preterm deliveries are common, with some studies reporting as high as 30-50% of parturient delivering before 36 weeks of gestation, with an average gestational age of 34 weeks. The compromised immune system of these women also may lead to perinatal complications. Studies have found a high rate of complications within 1-2 days postdelivery, a short median time for postnatal infection and a prolonged hospital stay. (OR 16; 95% CI, 1.6-165.60). Fortunately, the overall incidence of complications may be on the decreasing trend, as demonstrated by a decade-long study by the University of Southern California. The authors found a fall in maternal mortality from 4.1% to 1.7%, decrease in foetal and perinatal mortality from 52.7% to 22.75%, with improvement in average gestational age from 34.7 weeks to 37.4 weeks. Therefore, it appears evident that pregnant patients with SCD can have multiple complications and require good anaesthetic and intensive care.
Impact on Foetus: Poor intrauterine growth indicates placental insufficiency, resulting in delayed foetal growth and is associated with poor foetal outcomes. Microvascular damage and reduced uteroplacental circulation in these mothers lead to an exaggerated risk of spontaneous abortions and stillbirths. SCD is associated with increased risk for prematurity, low birth weight, small for gestational age (SGA), IUGR and perinatal mortality. Infants with SGA have high rates of neurodevelopmental delay, poor school performance, obesity and other metabolic diseases. IUGR is reported five times high in babies of parturient with SCD than without SCD. Also, the risk of prematurity among babies of women with SCD is increased two times to the babies of women without SCD, occurring in 31%–36% of pregnancies. However, the perinatal deaths and stillbirth rates vary widely, depending upon the country's health infrastructure and economic resources. In a country like Canada and the United Kingdom, the still birth rates are 1.6 per 1000 deliveries and 2.9 per 1000 deliveries, respectively, which was higher in comparison with the general population, even though they are developed nations. Moreover, in poor countries, stillbirth is found to be five times higher than the general population.,
| Perioperative Management of Patient with SCD|| |
Provision of antenatal care is linked to improved maternal and foetal outcomes. A multidisciplinary team comprising of obstetricians, haematologists and a nurse, trained in high-risk antenatal care should be involved in the care of such patients [Table 3].
Apart from managing sickle cell crises and pain during pregnancy, the main role of the anaesthesiologist is in the peripartum period, from managing labour analgesia to providing anaesthesia for caesarean delivery and postoperative pain management. Thus, a careful assessment of all organ systems is necessary for judicious and safe management.
The goal of the assessment is to determine the risk of peripartum SCD complications and organ dysfunction. A careful history and examination should be done to assess the disease severity such as transfusion history, number of hospital admission and timing of the crisis in pregnant patients. History of acute exacerbations of SCD or sickle cell crises indicates disease activity and severity. Frequent hospitalizations during pregnancy are independent predictors of perioperative VOC. A history of cardiac or pulmonary disease also adds to the risk factors. Specific patient characteristics like advanced age and infection add to the risk of VOC and ACS.
A detailed haematological evaluation is required. Complete blood count may reveal neutropenia in patients on hydroxyurea therapy. Haemoglobin electrophoresis reveals the percentage of HbS and helps in deciding on the need for prophylactic BT. As discussed, the role of BT remains a contentious issue and the final decision should be taken in consultation with a haematologist and obstetrician along with the patient as post-transfusion complications during pregnancy can indirectly affect neonates by inducing hypoxia and prevent the women to receive further transfusion [Table 4].
|Table 4: Preoperative investigations in SCD with pregnancy and their significance|
Click here to view
Organ dysfunction resulting from SCD-related complications like sickle cell crisis, infections and repeated transfusions should be investigated. In patients with a history of recurrent chest infections or ACS, and those with obstructive or restrictive chest disease patterns, chest imaging and pulmonary function testing may be needed. Cardiac status workup including electrocardiogram and echocardiography should be performed to rule out congestive cardiac failure and pulmonary hypertension due to longstanding anaemia. Oxygen saturation and arterial blood gas analysis is useful and baseline oxygen saturation should be noted in the preanaesthetic clinic. This may also help rule out methaemoglobinemia, which can frequently co-exist and lead to false readings of oxygen saturation., Chronic renal dysfunction may be seen in SCD patients and should be investigated. As these women are likely to have received multiple transfusions, blood must be screened for various alloantibodies and extensive cross-matching must be done before BT. Adequate blood products should be arranged for replacement during delivery. Parturients admitted for emergency surgery require special consideration as the risk of sickle crisis is more likely to be precipitated.
Labour analgesia in SCD with pregnancy
All parturients should be followed for an anaesthetic assessment as a routine in the third trimester and if high-risk, should be referred at an earlier stage. Obstetric anaesthesiologists should be informed regarding admission of the patient in sickle crisis during pregnancy or whenever labour begins as the parturient in labour has a high chance of going into the sickle cell crisis., This is due to considerably raised oxygen consumption, blood loss and vasoconstriction during labour. Therefore, an effective labour analgesia plan is an integral part of the management of the labouring parturient with SCD.
Central neuraxial analgesia is the gold standard for labour analgesia and it includes epidural and combined spinal-epidural analgesia (CSE). Epidural analgesia is ideal for labour pain especially in parturient with opioid tolerance or sickle related pain in the lower body. Local anaesthetics used here cause sympathetic block, which in turn causes vasodilation and enhanced blood flow, thus avoiding sickle cell crisis. Finer et al. reported successful use of epidural analgesia for labour pain and sickle cell crisis. Similarly, other authors have also reported the successful use of CSE and epidural for labour analgesia as well as management of sickle cell crisis., Apart from regional techniques, another effective option is entonox (50% N2O: 50% O2). Entonox can be used in SCD with pregnancy for monitoring of oxygen saturation but is not to be given for long durations due to neurobehavioural hazards of nitrous oxide on neonates. The use of nonpharmacological methods in labour for these patients has limited data available and requires further research.
Anaesthesia for caesarean section
In addition to a thorough preoperative assessment, certain precautions must be exercised while preparing these parturients for caesarean delivery. Whenever possible, the parturient should be admitted at least 1 day before the surgery. These patients are at a high risk of getting pulmonary infections as a result of repeated hospitalizations, subclinical lung infarctions and an immunocompromised condition resulting from splenic involvement. Thus, chest physiotherapy should be initiated preoperatively and continued postoperatively, in addition to administration of prophylactic antibiotics. Good hydration status must be maintained along with minimal preoperative fasting period, to decrease blood viscosity and the tendency of sickling. Oral hydration is preferred and clear fluids up to 1–2 hours before surgery is recommended. Intravenous fluids are considered in case oral hydration is inadequate. The basic principle in these patients is to avoid conditions that encourage sickling. Thus, it is imperative to avoid hypothermia, hypoxemia, hypovolaemia, acidosis and hypotension. Adequate hydration, optimal ventilation, robust analgesia, anxiolysis and antibiotic prophylaxis may help mitigate the chances of complications.
Regional anaesthesia in these patients may offer certain advantages such as superior intraoperative and postoperative analgesia, better peripheral blood flow due to sympathetic blockade, and avoidance of intubation [Table 5]. Bakri et al. advocated for regional anaesthesia for caesarean delivery in SCD parturients, reporting lower opioid consumption, better analgesia and less VOC episodes as compared with patients receiving general anaesthesia (GA). Disadvantages include hypotension and venous stasis in the peripheries, which can cause sickling and can precipitate VOC. If needed, vasopressors can be used to treat hypotension. While vasoconstricting drugs like ephedrine can reduce the blood flow in vascular beds, there has been no evidence of postnatal sickling complications in SCD parturients, and they can be used for treating hypotension following spinal anaesthesia.,, Thus, regional anaesthesia is largely safe for caesarean section in SCD, with precautions like adequate hydration, avoidance of hypotension and careful monitoring of the level of the block to prevent respiratory depression.
General anaesthesia (GA) carries the advantages of better titration of blood pressure, better oxygenation with controlled ventilation and robust anxiolysis, all of which can help prevent factors responsible for sickling crises. Whenever GA is administered, special attention should be paid to effective oxygenation during intubation. Passive oxygenation using nasal cannulae or high flow nasal oxygenation prolong the apnoeic period before commencement of desaturation. Preoxygenation must be practised and hypotension avoided with careful titration of induction agents. In obese parturients, ramping should be considered to optimize the position for intubation. Long-acting opioids and muscle relaxants should be avoided. Intraoperatively, normocarbia, normothermia and normal haemodynamics should be maintained. Fluids should be used judiciously depending on the preoperative cardiac status and blood loss should be replaced timely with blood products. Maintenance of temperature with prewarmed fluid and warming blankets is essential, as shivering and peripheral vasoconstriction can cause hypoxia and increased sickling., In addition to ASA Standard monitoring, neuromuscular monitoring should be practised ensuring full reversal before tracheal extubation.
Overall, no particular anaesthetic technique has shown marked benefit over others. The evidence suggests that in an otherwise healthy parturient with well-preserved cardiopulmonary status and mild anaemia, regional anaesthesia should be preferred with the aforementioned precautions. In severely anaemic, decompensated parturients or those in whom postoperative ICU stay is planned, GA may be a better option due to better haemodynamics and ventilation control. The choice of anaesthesia technique is not as important as the care with which it is administered, and the anaesthetist must form a meticulous anaesthesia plan bearing the above principles in mind.
Pain is the dominant clinical feature throughout the course of SCD. Apart from labour, analgesia is required for the postoperative period, pain due to VOC and in certain associated chronic conditions like leg ulcers, avascular necrosis, and so on. A multimodal approach, consisting of a combination of local or regional blocks, oral and intravenous drugs, patient-controlled intravenous or epidural analgesia, and nurse-controlled analgesia, is recommended. Opioids remain the mainstay for the treatment of VOC as well as for postoperative pain in patients with SCD., One must be cautious for side-effects especially nausea and vomiting that can confound the diagnosis of an acute abdomen in VOC as well as sedation and delayed respiratory depression, which can itself precipitate VOC. Due to the chronic nature of pain in SCD patients, opioid tolerance, dependence and addiction is common among SCD patients, and are an important limitation.
Non-steroid anti-inflammatory agents (NSAIDs) and acetaminophen are commonly the most used drugs for patients with SCD with mild to moderate pain. Acetaminophen is safe and effective for postoperative pain, but its role in VOC is unclear. Numerous studies have failed to show any benefit of NSAIDs in treating VOC, but they remain an important part of chronic pain management, especially in combination with opioids. Side-effects such as oligohydramnios and early closure of the ductal arteriosus, apart from gastritis, kidney dysfunction and antiplatelet activity should also be kept in mind with NSAID use.,
Ketamine, an NMDA antagonist, is considered in severe pain unresponsive to standard therapy and in patients with opioid tolerance or opioid-induced hyperalgesia, which are common with VOC pain.,, Recent studies have suggested that low-dose ketamine may be effective in decreasing opioid consumption in patients with VOC. However, ketamine is a psychomimetic drug and can influence foetal outcomes.
Epidural analgesia has a good role in treating painful VOC as well as treating perioperative pain and labour pain. Patient controlled epidural analgesia (PCEA) is more effective than intermittent analgesia for the treatment of VOC pain. Certain regional blocks have also been shown to have an advantage in postoperative analgesia in pregnant patients with SCD that includes bilateral transversus abdominus plane block and ilioinguinal-ilio hypogastric nerve block.
About half of the women with SCD experience VOC in the postpartum period leading to a high risk of decompensation of SCD due to blood loss, dehydration and pain. Thus, the first 48 hours requires close monitoring in the postpartum period. The degree of anaemia must be assessed following the intrapartum blood loss in both normal deliveries and caesarean sections. Blood should be replaced adequately and timely to avoid sickling. Patients with SCD have compromised urinary concentrating ability and become dehydrated easily, which may also increase the risk of deep vein thrombosis in the parturient with SCD. So, thromboprophylaxis hydration and early mobilization may reduce the risk of thromboembolism. Thromboprophylaxis with low molecular weight heparin is recommended for 7 days after vaginal delivery or a period of 6 weeks following caesarean section. Antithrombotic stockings are recommended during the puerperium period., Patients are more susceptible to postoperative respiratory complications and wound infection. So. antibiotic prophylaxis should be administrated as per local policy along with postoperative chest physiotherapy. Any crisis at this time should be managed as in nonpregnant adults. NSAIDS are routinely recommended in the postpartum period. Some patients may require high doses of opioids having developed opioid tolerance due to frequent use.
| Sickle Cell Trait in Pregnancy|| |
SCT has a benign clinical picture and most patients with SCT live normal healthy lives as red blood cells do not sickle till PaO2 drops <15 mmHg and show sickling only under extraordinary physiological conditions. Therefore, the life span of RBC is normal. No haematological manifestations are usually present, and mild abnormalities when present are mostly subclinical. Pregnant patients may be slightly more susceptible to asymptomatic bacteriuria, pyelonephritis and in some cases, haematuria. Other complications including splenic infarction at high altitude, venous thromboembolism, and chronic renal disease have been reported in SCT, but are extremely rare., SCT is also linked with adverse outcomes in pregnancy like pre-eclampsia and prematurity. No specific therapy is required, and the same principles that guide the management of SCD with pregnancy apply to those with SCT also. We suggest close antenatal follow-up, keeping a low threshold for hospitalization, and haematinic therapies if needed.
Covid-19 and SCD
During the COVID-19 pandemic, emerging data suggests that pregnant patients with SCD have been included in the 'high-risk' category of the population. Patients may present with VOC due to covid-19 infection and are prone to superimpose bacterial infection due to impaired immunity resulting from functional hyposplenism, systemic vasculopathy, which predisposes them to end-organ dysfunction, and high risk for thrombosis. A recent review of COVID-19 in pregnant women revealed some cases of severe maternal morbidity and perinatal deaths, though the majority of the cases had a good outcome. But. another research reported that severe respiratory complications (ARDS) and multiple organ failure are common in SCD pregnant women, so management should be according to standard covid protocols and potentially life-saving interventions such as respiratory support depending on pre-existing co-morbidities., However, limited data has been published regarding covid-19 infections in pregnant women with SCD.
| Conclusions|| |
SCD is an inherited disease with multisystem complications and pregnancy has been associated with exacerbation of disease leading to additional risk of obstetric and foetal complications. Appropriate management of pregnancy with SCD should be best accomplished in close supervision with a multi-disciplinary team. Factors that increase sickling should be avoided during the peripartum period. Protocol based on national guidelines should be followed and assessed individually in the parturient. Information, education and communication sessions during antenatal visits essentially minimize peripartum risks and complications.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wilson M, Forsyth P, Whiteside J. Hemoglobinopathy and sickle cell disease. Continuing Educ Anaesth Crit Care Pain 2010;10:24-8
Dormandy E, James J, Inusa B, Rees D. How many people have sickle cell disease in the UK? J Public Health 2018;40:291–5.
Urade BP. Sickle cell gene scenario in tribal India. J Health Med Inform 2012;3:114.
Ministry of Health and Family Welfare Government of India. Prevention and control of hemoglobinoparthies in India-Thalassemia, Sickle cell disease and other variant hemoglobins. National Health Mission guidelines on hemoglobinopathies in India. 2016.
Rappaport VJ, Velazquez M, Williams K. Hemoglobinopathies in pregnancy. Obstet Gynecol Clin North Am 2004;31:287-317.
Inusa BP, Hsu LL, Kohli N, Patel A, Ominu-Evbota K, Anie K, et al
. Sickle cell disease- Genetics, pathophysiology, clinical presentation and treatment. Int J Neonatal Screen 2019;5:20.
Ware RE, De Montalembert M, Tshilolo L, Abboud MR. Sickle cell disease. Lancet 2017;390:311-23.
Gladwin M. Cardiovascular complications and risk of death in sickle cell disease. Lancet 2016;387:2565–74.
Veluswamy S, Shah P, Denton C, Chalacheve P, Khoo MCK, Coates TD. Vaso-occlusion in sickle cell disease: Is autonomic dysregulation of the microvasculature the trigger? J Clin Med 2019;8:1690.
Streetly A, Sisodia R, Dick M, Latinovic R, Hounsell K, Dormandy E. Evaluation of newborn sickle cell screening programme in England: 2010–2016. Archives of disease in childhood 2018;103:648-53.
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al
. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 1994;330:1639-44.
Firth PG, Head CA, Warltier DC. Sickle cell disease and anesthesia. Anesthesiology 2004;101:766–85.
Serjeant GR, Ceulaer CD, Lethbridge R, Morris J, Singhal A, Thomas PW. The painful crisis of homozygous sickle cell disease: Clinical features. Br J Haematol 1994;87:586-91.
Khurmi N, Gorlin A, Misra L. Perioperative considerations for patients with sickle cell disease: A narrative review. Can J Anaesth 2017;64:860-9.
Koshy M, Burd L, Wallace D, Moawad A, Baron J. Prophylactic red-cell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study. N Engl J Med 1988;319:1447-52.
Gladwin MT, Vichinsky E. Pulmonary complications of sickle cell disease. N Engl J Med 2008;359:2254–65.
Atz AM, Wessel DL. Inhaled nitric oxide in sickle cell disease with acute chest syndrome. Anesthesiology 1997;87:988–90.
Reardon DA, Dresemann G, Taillibert S, Campone M, van den Bent M, Clement P, et al
. Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer 2009;101:1995–2004.
Ballas SK, McCarthy WF, Guo N, DeCastro L, Bellevue R, Barton BA, et al
. Multicenter study of hydroxyurea in sickle cell anemia. Exposure to hydroxyurea and pregnancy outcomes in patients with sickle cell anemia. J Natl Med Assoc 2009;101:1046-51.
Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, et al
. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: Risks and benefits up to 9 years of treatment. JAMA 2003;289:1645-51.
No GT. Management of sickle cell disease in pregnancy. London: Royal College of Obstetricians and Gynaecologists. 2011 Jul.
Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, et al
. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med 2017;376:429-39.
Van Zuuren EJ, Fedorowicz Z. Low-molecular-weight heparins formanagingvaso-occlusive crises in people with sickle cell disease. Cochrane Database Syst Rev 2013;6:CD010155.
Heeney MM, Hoppe CC, Abboud MR, Inusa B, Kanter J, Ogutu B, et al
. A multinational trial of prasugrel for sickle cell vaso-occlusive events. N Engl J Med 2016;374:625–35.
Adam SS, Hoppe C. Potential role for statins in sickle cell disease. Pediatr Blood Cancer 2013;60:550–7.
Chou ST. Transfusion therapy for sickle cell disease: A balancing act. Hematology Am Soc Hematol Educ Program 2013;2013:439-46.
Chou ST, Fasano RM. Management of patients with sickle cell disease using transfusion therapy: Guidelines and complications. Hematol Oncol Clin North Am 2016;30:591–608.
Vichinsky EP, Haberkern CM, Neumayr L, Earles AN, Black D, Koshy M, et al
. A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group. N Engl J Med 1995;333:206-13.
Haberkern CM, Neumayr LD, Orringer EP, Earles AN, Robertson SM, Black D, et al
. Cholecystectomy in sickle cell anemia patients: Perioperative outcome of 364 cases from the National Preoperative Transfusion Study. Preoperative Transfusion in Sickle Cell Disease Study Group. Blood 1997;89:1533-42.
Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J, Koshy M, et al
. The perioperative complication rate of orthopedic surgery in sickle cell disease: Report of the National Sickle Cell Surgery Study Group. Am J Hematol 1999;62:129-38.
Howard J, Malfroy M, Llewelyn C, Choo L, Hodge R, Johnson T, et al
. The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study: A randomised, controlled, multicentre clinical trial. Lancet 2013;381:930-8.
Estcourt LJ, Fortin PM, Trivella M, Hopewell S. Preoperative blood transfusions for sickle cell disease. Cochrane Database Syst Rev 2016;4:CD003149.
Chou ST, Jackson T, Vege S, Smith-Whitley K, Friedman DF, Westhoff CM. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood 2013;122:1062-71.
Porter J, Garbowski M. Consequences and management of iron overload in sickle cell disease. Hematology Am Soc Hematol Educ Program 2013;2013:447-56.
Scheunemann LP, Ataga KI. Delayed hemolytic transfusion reaction in sickle cell disease. Am J Med Sci 2010;339:266-9.
Hoban MD, Orkin SH, Bauer DE. Genetic treatment of a molecular disorder: Genetherapy approaches to sickle cell disease. Blood 2016;127:839–48.
Cavazzana M, Ribeil JA, Payen E, Suarez F, Beuzard Y, Touzot F, et al
. Outcomes of gene therapy for severe sickle disease and beta-thalassemia major via transplantation of autologous hematopoietic stem cells transduced ex vivo with a lentiviral beta AT87Q-globin vector. 2015; 202:202
Canver MC, Orkin SH. Customizing the genome as therapy for the β-hemoglobinopathies. Blood, The Journal of the American Society of Hematology 2016;127:2536-45.
Camous J, N'da A, Etienne-Julan M, Stéphan F. Anesthetic management of pregnant women with sickle cell disease—Effect on postnatal sickling complications. Obstet Anesth Dig 2008;28:230.
Firth PG. Anesthesia and hemoglobinopathies. Anesthesiol Clin 2009;27:321-36.
Powars DR, Sandhu M, Niland-Weiss J, Johnson C, Bruce S, Manning PR. Pregnancy in sickle cell disease. Obstet Gynecol 1986;67:217-28.
Koshy M, Chisum D, Burd L, Orlina A, How H. Management of sickle cell anemia and pregnancy. J Clin Apher 1991;6:230-3.
Daigavane MM, Jena RK, Kar TJ. Perinatal outcome in sickle cell anemia: A prospective study from India. Hemoglobin 2013;37:507-15.
Billett HH, Langer O, Regan OT, Merkatz I, Anyaegbunam A. Doppler velocimetry in pregnant patients with sickle cell anemia. Am J Hematol 1993;42:305-8.
Boafor TK, Olayemi E, Galadanci N, Hayfron-Benjamin C, Dei-Adomakoh Y, Segbefia C, et al
. Pregnancy outcomes in women with sickle-cell disease in low and high income countries: A systematic review and meta-analysis. BJOG 2016;123:691-8.
Meeks D, Robinson SE, Macleod D, Oteng-Ntim E. Birth weights in sickle cell disease pregnancies: A cohort study. PLoS One 2016;11:e0165238. doi: 10.1371/journal.pone. 0165238.
Whitley KM. Complications in pregnant women with sickle cell disease. Hematology Am Soc Hematol Educ Program 2019;2019:359-66.
Kuczkowski KM. Labour-induced sickle cell crisis in a previously asymptomatic parturient with sickle cell disease. Anaesthesia 2003;58:1044-5.
Walker I, Trompeter S, Howard J, Willians A, Bell R, Bingham R, et al
. Guideline on the peri-operative management of patients with sickle cell disease. Anaesthesia 2021;76:805-17.
Finer P, Blair J, Rowe P. Epidural analgesia in the management of labor pain and sickle cell crisis--A case report. Anesthesiology 1988;68:799-800.
Howard J, Oteng-Ntim E. The obstetric management of sickle cell disease. Best Pract Res Clin Obstet Gynaecol 2012;26:25-36.
Bakri MH, Ismail EA, Ghanem G, Shokry M. Spinal versus general anesthesia for Cesarean section in patients with sickle cell anemia. Korean J Anesthesiol 2015;68:469-75.
Mushambi MC, Kinsella SM, Popat M, Swales H, Ramaswamy KK, Winton AL, et al
. Obstetric anaesthetists' association and difficult airway society guidelines for the management of difficult and failed tracheal intubation in obstetrics. Anaesthesia 2015;70:1286–306.
Checketts MR, Alladi R, Ferguson K, Gemmell L, Handy JM, Klein AA, et al
. Recommendations for standards of monitoring during anaesthesia and recovery 2015: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia 2016;71:85–93.
Brandow AM, Carroll CP, Creary S, Edwards-Elliott R, Glassberg J, Hurley RW, et al
. American Society of Hematology 2020 guidelines for sickle cell disease: Management of acute and chronic pain. Blood Adv 2020;4:2656-701.
Elsayegh D, Shapiro JM. Sickle cell vasoocclusive crisis and acute chest syndrome at term pregnancy. South Med J 2007;100:77-9.
Zempsky WT. Evaluation and treatment of sickle cell pain in the emergency department: Paths to a better future. Clin Pediatr Emerg Med 2010;11:265-73.
Tawfic QA, Faris AS, Kausalya R. The role of a low-dose ketamine-midazolam regimen in the management of severe painful crisis in patients with sickle cell disease. J Pain Symptom Manage 2014;47:334-40.
Santos J, Jones S, Wakefield D, Grady J, Andemariam B. Patient controlled analgesia for adults with sickle cell disease awaiting admission from the emergency department. Pain Res Manag 2016;2016:3218186.
Ahemed SA, Denu ZA, Getinet Kassahun H, Yilikal Fentie D. Efficacy of bilateral transversus abdominis plane and ilioinguinal-iliohypogastric nerve blocks for postcaesarean delivery pain relief under spinal anesthesia. Anesthesiol Res Pract 2018;2018:1948261.
Jain D, Atmapoojya P, Colah R, Lodha P. Sickle cell disease and pregnancy. Mediterr J Hematol Infect Dis 2019;11:e2019040. doi: 10.4084/MJHID.2019.040.
Gibson JS, Rees DC. How benign is sickle cell trait? EBioMedicine 2016;11:21-2.
Wilson S, Ellsworth P, Key NS. Pregnancy in sickle cell trait: What we do and don't know. Br J Haematol 2020;190:328-35.
Inparaj S, Buckingham M, Oakley L, Seed PT, Lucas S, Oteng-Ntim E. Pulmonary complications for women with sickle cell disease in pregnancy: Systematic review and meta-analysis. Thorax 2020;75:568-75.
Justino CC, Campanharo FF, Augusto MN, Morais SC, Figueiredo MS. COVID-19 as a trigger of acute chest syndrome in a pregnant woman with sickle cell anemia. Hematol Transfus Cell Ther 2020;42:212-4.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]