Anaesthetic management of beta thalassemia major with hypersplenism for splenectomy in pediatric age group: Report of four cases.

Beta thalassemia is the most common cause of hemolytic anemia in India. Hereby we are reporting four cases of beta thalassemia major aged between 5 and 10 years posted for splenectomy over a period of 2 months. These patients were on repeated blood transfusions since the day of diagnosis, and two patients had a history of cardiac failure. In addition to emphasizing the anesthetic challenges, the purpose of reporting such cases is to raise the awareness of the disease and prevention of the same by aggressive screening and prenatal diagnosis.

INTRODUCTION

Thalassemias are hereditary disorders characterized by a reduction in the synthesis of globin chain (α or beta) in hemoglobin (Hb) molecule.[1] Splenectomy is a common surgery performed in children of beta thalassemia major to reduce the frequency of transfusion and mechanical effect of enlarged spleen. Anesthetic management of these children is challenging being associated with unanticipated difficult airway, perioperative high blood pressure (BP), iron overload, endocrinological abnormalities, cardiac diseases, restrictive respiratory pattern and pulmonary hypertension.[2]

We present cases, which highlight anesthetic concerns in children of beta thalassemia major with hypersplenism posted for splenectomy.

CASE REPORTS

Case 1

A 5-year-old male child, weighing 14 kg born of nonconsanguineous marriage, diagnosed as beta thalassemia major at the age of 6 months was on multiple blood transfusions with increasing frequency from once a month to once a week presently.

On perioperative examination, child had frontal bossing, depressed nasal bridge, malar prominence and high arched palate. Airway assessment was found normal and mallampatti grade 3. He was pale, icteric and febrile with heart rate (HR) of 121 bpm. BP of 110/60 mmHg, respiratory rate of 34 cycle/min and oxygen saturation of (SpO2) 94% on room air. He had prominent neck veins and pedal edema. Systemic examination revealed ejection systolic murmur of grade III, clear lung fields, hepatomegaly 8 cm below right costal margin and splenomegaly 12 cm below left costal margin (LCM).

Hematological investigations revealed Hb of 5.8 g% after 49th transfusion, total counts 12,000/cm3 and platelet count of 80,000/cm3. Peripheral blood smear revealed hemolytic anemia with thrombocytopenia and electrophoresis: HbA: 3.9%, HbA2: 5.9%, HbF: 82.7%. HbS: 4.7% and HbD: 2.8%. Sickling test was negative, and serum ferritin 1200 ng/ml (N 17–140 ng/ml) liver function tests, renal function tests, coagulation profile and serum electrolytes were within normal limits. Two dimensional echo findings were dilated right atrium, ventricle and pressure gradient across pulmonary artery of 86 mmHg. Ultrasonography showed splenomegaly 18 cm below LCM. Hb electrophoresis of his parents revealed that both were beta thalassemia trait with HbA2 72.3% (father) and 81.7% (mother).

Previously this child was treated conservatively 3–4 times for acute cardiac failure last episode being 1-week prior to surgery. Child was on tablet frusemide 5 mg BD. He had received pneumococcal, meningococcal and haemophilus influenza vaccination 7 days prior to surgery.

Surgery was done under general anesthesia. His baseline parameters were BP 110/60 mm Hg, HR 124 bpm and SpO2 of 96%. Child was premedicated with injection midazolam 1 mg, fentanyl 50 μg and Glycopyrrolate 0.1mg and was induced with injection ketamine 30 mg and succinylcholine 30 mg. Direct laryngoscopy examination showed Cormack Lehane grading of class IIB; endotracheal tracheal intubation was performed with the help of stylet using uncuffed endotracheal tube 5 mm. Under anesthesia right jugular vein and right radial artery were cannulated. Precautions were taken to prevent air embolism. BP showed a trend toward hypertension intra operatively with systolic BP around 140 mmHg (baseline of 110 mmHg) and diastolic BP 90 mmHg (baseline 60 mmHg). Anesthesia was maintained with injection propofol 50mcg/kg/min, O2:N2O 2:2 and intermittent boluses of vecuronium. Estimated blood loss was 250 ml and replaced with 400 ml of ringer lactate and 300 ml of whole blood. Paracetamol suppository 170 mg was inserted for postoperative analgesia Figure 1.

Figure 1

Child with massive splenomegaly under general anesthesia

With the return of adequate respiratory efforts neuromuscular blockade was reversed with an intravenous neostigmine 0.75 mg and glycopyrrolate 0.15 mg and extubated after thorough throat suctioning. Child was transferred to Pediatric Intensive Care Unit for observation and monitoring. Hb improved gradually to 9 g% and platelet count to 1 lakh/mm3 and was discharged 7 days later from ward.

Case 2

A 5-year-old male child, weighing 12 kg, diagnosed as thalassemia major at the age of 4 years, with a progressive pallor and easy fatiguability was admitted to our hospital. On examination, he had puffiness of the face and abdominal distension; he was started on syrup digoxin 75 mcg BD and was tapered to 10 mcg/kg/day. After few days when he was posted for splenectomy, vitals were stable, systemic examination was normal. Hb had improved to 8.3 g% after two blood transfusions. Surgery was done under general anesthesia, and perioperative course was uneventful.

Case 3

A 10-year-old male child, diagnosed with thalassemia major at age of 6 years, was on regular blood transfusions (around 25 transfusions till admission). He was born of second degree consanginous marriage. He was posted for splenectomy and on preoperative examination, vitals were stable. Airway examination showed Mallampati grade II. Hb was 8.7 g%, and other laboratory investigations were normal. Surgery was done under general anesthesia, and course was uneventful.

Case 4

A 6-year-old female child, weighing 13 kg was diagnosed with thalassemia major when she was 8 month old. She was regularly treated with blood transfusions (about 27 till admission). She had a history of cardiac failure. On preoperative examination, vital signs and laboratory investigations were normal. She had frontal bossing and malar prominence, airway on examination was Mallampati grade II [Table 1].

Table 1

Preoperative and intraoperative findings

DISCUSSION

Worldwide 15 million people have clinically apparent thalassemia. The frequency of beta thalassemia trait in India, an ethnically diverse country with a population of 1.2 billion, varies from 1% to 17% with an average of 3.3%.[3] The calculation according to birth incidence indicates that, in India, approximately 11,300 homozygous thalassemics are added to the existing load of thalassemics every year.[3] Prevention is not only a good public health measure, but also cost effective as the ratio of cost of treatment to prevention is 4:1.[4] Education, awareness, prenatal screening and counseling, genetic counseling are not being effective enough in a developing country like ours. It is necessary to set up preimplantation genetic diagnosis and noninvasive prenatal diagnosis centers. Aggressive screening of a pregnant woman can bring down the burden of this disease.

The term thalassemia is derived from Greek, thalassa (sea) and haima (blood).[5] beta thalassemia major is characterized by impaired production of beta globin chains.[6] This imbalance of globin chain synthesis (α>>beta) results in intravascular hemolysis, profound anemia, erythroid hyperplasia, extramedullary hematopoiesis, hepatospleenomegaly, severe bone deformities, growth retardation and death by second or third decade.

The chronic hemolysis and disturbed nitric oxide physiology can lead to progressive vascular damage and pulmonary hypertension.[2] Extramedullary hematopoiesis resulting in maxillary bone enlargement causes difficulty in airway management.[2] Preoperative evaluation should focus on organs affected by hemochromatosis following multiple transfusions such as cardia, liver and endocrine system (pancreas and pituitary). Management of beta thalassemia is mainly supportive such as frequent blood transfusions, splenectomy if there is splenomegaly and treatment of transfusion caused iron overload. Allogenic bone marrow (stem cell) transplantation in severely affected patients can result in the cure.[7] Splenectomy is usually needed around 6–8 years of age when transfusion requirement is 1.5 times the normal. Usually, it is delayed till 5 years as there is a risk of sepsis.[8]

Most of the case reports in international journals are about adults with beta thalassemia intermedia (milder disease) undergoing splenectomy.[910] These authors discuss about the perioperative problems such as severe anemia, potential difficult airway, perioperative hypertension, etc., There is a report using fiberoptic bronchoscopy in a patient with long-standing thalassemia major.[11] There are case reports about anesthetic management in patients with thalassemia with other diseases like systemic lupus erythematosus, hypothyroidism and eisenmenger's syndrome.[612]

We report here anesthetic management in 4 cases of beta thalassemia major undergoing splenectomy, all in pediatric age group as India is endemic to thalassemia. All of them were diagnosed in early childhood (case 1 as early as 5 months of age) and had a history of frequent blood transfusions with marked splenomegaly. Cases 1 and 4 had a history of treatment for cardiac failure and had high pulmonary artery pressures. Challenges for anesthesiologists in such patients would be management of anemia (which persists in spite of transfusion), difficult airway (due to extramedullary hematopoiesis), pulmonary hypertension and intra operative systemic hypertension severe V/Q mismatch due to restrictive lung disease caused by hypersplenism and decreased oxygen carrying capacity (severe anemia). There is a high incidence of blood transfusion related diseases like hepatitis hence precaution must be taken to avoid exposure to blood and body fluids.[1]

In our patients, preoperative Hb ranged from 4.7% to 9.8% and blood transfusions were carried out as per the requirements. None of our patients received iron chelation therapy, which is actually beneficial in preventing cardiac dysfunction and reducing liver iron concentrations.

During perioperative period, hypoxia, cardiovascular depression should be avoided.[1] Keeping above goals in mind we used combination of fentanyl and low dose of ketamine for induction. Difficult intubation with Cormack Lehane IIB was seen in cases 1 and 4, those with the longest history of the disease. Intraoperative hypertension, cause of which is not clear, commonly seen in such patients. Repetitive blood transfusion throughout life and autotransfusion during the splenectomy are considered as possible causes of raised BP.[1] We successfully managed the intra-operative hypertension by a judicious mix of volatile agents, propofol and occasional beta blockers. We used both invasive BP and central venous pressure (CVP) monitoring because of pulmonary artery hypertension. CVP was maintained at 8–10 cm H2O to avoid volume overload and right ventricular failure. Postoperative follow-up of patients revealed there was improvement in Hb% and decreased requirements of blood transfusions.

CONCLUSION

Hemoglobinopathies are large and diverse group of disorders that present with many interesting and challenging situations. Thalassemias, more common in developing countries like ours, are likely to benefit from specific gene therapy.[13] Close communication and collaboration between anesthesiologist, surgeon and hematologist is essential to ensure safe and optimum management of beta thalassemia major.