Patients with sickle cell disease (SCD) may
present to the anaesthesiologist for peri-operative care for
an elective or emergency surgery, management of an acute
painful crisis or intensive treatment for acute respiratory
failure. We describe the successful management of a young male
patient with SCD, who presented in crisis, posted for
laparoscopic cholecystectomy under general anaesthesia.
Preoperative optimization and careful anaesthetic planning is
of prime importance.
Keywords: sickle cell crisis, cholecystectomy,
exchange transfusion, analgesia
Introduction
Sickle cell disease (SCD) is a complex clinical entity
characterized by an inherited chronic haemolytic anaemia
associated with variable number of acute painful
vaso-occlusive episodes [1]. Over 30 million people worldwide
have SCD with the high concentration of the disease among
persons of African, Middle Eastern and central Indian ancestry
[2-3]. Polymerization of haemoglobin S (HbS) after
de-oxygenation is the fundamental molecular event that
underlies the protean clinical manifestation of SCD [4].
Polymerised HbS confers a characteristic sickle shape to the
RBC, in association with other cellular alterations;
furthermore, these RBCs are more likely to rupture, releasing
damaging cell-free haemoglobin (Hb) into the circulation
(haemolysis), with significant consequences that include
vascular nitric oxide (NO) consumption and oxidative stress
[5]. Process of polymerization is triggered and/ or enhanced
by hypoxia, vascular stasis, infection, inflammation,
increased blood viscosity, vasoconstriction, dehydration,
hypotension, stress, cold temperature, acidosis and decreased
flow [6,7]. Cholelithiasis is the well recognized complication
of chronic haemolysis. About 7% of all deaths among patients
with sickle cell anaemia are related to surgery [8]. Surgical
procedures in sickle cell patients have been associated with
relatively increased risks of peri-operative mortality,
vaso-occlusive crisis, acute chest syndrome, post operative
infections and congestive heart failure [9,10]. We had planned
anaesthesia and analgesia of this patient to avoid
vaso-occlusive episodes and prevent complications.
Case report
A young male patient, who was diagnosed to have sickle cell
anemia with homozygous trait two and a half decades back,
presented to the hospital with complaints of generalised
weakness, abdominal pain and yellowish discoloration of eyes
since one week.
The abdominal pain was over the right upper quadrant which was
cramping in nature, it was intermittent and lasting for few
hours, radiating to upper back between the shoulder with no
apparent aggravating or relieving factors and no relation to
food intake. It was associated with nausea, vomiting and heart
burn. He had 3 episodes of vomiting which was bilious in
nature. He had progressive yellowish discoloration of eyes and
skin since past one week. It was not associated with pruritis
or loose stools. He also complained of high coloured urine
since the past two weeks. He had high grade fever on admission
which started 2 days back. It was intermittent in nature not
associated with chills or rigors. He was prescribed oral
hydroxyurea, folic acid and antibiotic prophylaxis with
intravenous cefotaxim, metronidazole. Patient also received IV
Tramadol 100 mg b.d and inj Fentanyl bolus 100 mcg for
analgesia. Ultrasound abdomen showed distended gall bladder
with sludge a large 17 mm stone present with gall bladder wall
thickening and edema noted. No pericholecystic collection, No
CBD stone. He was hence posted for laparoscopic
cholecystectomy.
Patient gave a history of sickle cell disease which was
diagnosed at the age of 10 years after evaluation for frequent
episodes of fever and weakness. Patient was advised to start
medication (Tab. Hydroxyurea) but he was noncompliant to
medication since the past 5 years. He has had 2 hospital
admissions in the past 5 years after complaints of acute back
pain, each admission lasting for 5 days of hospital stay. He
also gives a history of blood transfusions in the past
admissions.
Patient did not give any history of any known co-morbidities.
He did not give any recent history suggestive of respiratory
infection or joint pain, chest pain suggestive of cardiac
involvement. He had moderate effort tolerance (METS >4)
prior to admission. He has not undergone any surgeries in the
past.
Patient gave a history of the sickle cell disease in younger
brother who passed away at the age of 10 years. He also has a
daughter who was diagnosed to have sickle cell disease at the
age of 5 years and is currently on Tab. Hydroxyurea.
On general examination, patient was moderately built and
nourished, he was icteric and had stable vital parameters with
regular pulse rate of 90 beats/min and blood pressure of
110/80 mmHg, right arm sitting position. Airway assessment
showed normal mouth opening, with a Mallampatti grade 2 and
adequate neck movements with sternomental distance of 12.5 cm.
Per abdomen examination revealed tenderness in right
hypochondrium, murphy's sign was positive. No visceromegaly.
All other systems were within normal limits.
His baseline investigations were as follows: Hb: 9.4 gm%,
Total count 20,800 cells/mm
3, neutrophil 95%,
platelet 3.6 lakh/mm
3, packed cell volume 28.3%,
retic count 7.8%, creatinine 0.8mg/dl, total bilirubin 6.6
mg/dl direct bilirubin 1.3mg/dl, indirect 15.0 mg/dl, LDH 52
U/L, peripheral smear showed sickle cell anemia in haemolytic
crsis with neutrophilia, Hb electrophoresis was done which
showed HbS 75.3%, HbF 11%,Hb A0 6.1% Hb A1c 3.8% Hb A2 of
3.4%. Baseline electrocardiogram and chest X-ray were within
normal limits. Since the HbS was 75.3%, after discussion with
the surgeon it was decided that owing to the risks involved it
is better to postpone the surgery until the level of HbS had
reduced. Hence, he underwent four partial exchange
transfusions. His antibiotics were stepped up to Inj.
Meropenem 1g 8th hourly. There was a serial reduction in the
values of HbS which came down to 55.3% and HbF of 7.7%
after the first partial exchange transfusion, then a HbS of
48.2% and HbF of 6.2%, followed by HbS of 41.9% and HbF of
5.1% and finally his HbS was 36.7%, HbA0 47.4%, HbF 4.4% HbA1c
5.1% Hb A2 3.1% prior to surgery. Hb was 11.2gm%, Total count
12300cells/mm3,neutrophil 80%,platelet 2.19 lakh/mm3, packed
cell volume 32.5%, sodium 136 mEq/L, potassium 3.6 mEq/L,
total bilirubin 31.6mg/dl, direct bilirubin 20.7 mg/dl.
Patient was started on incentive spirometry pre operatively.
He was kept fasting after 12 midnight and started on ringer
lactate 100ml/hour to avoid dehydration.
Patient received intravenous Midazolam 1mg, Ondansetron 4 mg,
Dexamethasone 8 mg and Glycopyrrolate 0.2 mg as pre medication
half an hour prior to surgery. On arrival to the operation
theatre for the scheduled laparascopic cholecystectomy, all
ASA standard monitors were attached. Pulse oximeter showed
room air saturation of 97%. Oxygen was administered via
Hudson's mask. Patient was draped in a warming blanket.
He was pre loaded with 1 litre of warm intravenous ringer
lactate. He was induced with inj fentanyl 200 mcg (titrated
doses), propofol 100 mg, lignocaine 60mg, precurarisation with
atracurium and succinyl choline 100mg. Rapid sequence
induction was performed as per the present COVID 19 protocol.
Intubation was done with Karl Storz videolaryngoscope. Airway
secured with 8 mm cuffed polyvinyl endotracheal tube fixed at
21 cm lip level after confirming bilateral equal air entry.
Following which 50 mg Atracurium was given intravenously.
Endotracheal cuff pressure was 24 cmH20. Patient's stomach was
deflated using a suction catheter of size 14. Patient
was mechanically ventilated using closed circuit and ET CO
2
monitoring (end tidal carbon dioxide) with volume control
ventilation (VCV) (tidal volume: 550 ml, respiratory rate
14/minute, PEEP 5 cmH
20, FiO
2 of 45%).
Utmost care was taken during induction to avoid hypotension
and hypoxia. ABG was done which was normal. An invasive
arterial line was introduced into the left radial artery. A
temperature probe was introduced for monitoring which was
maintained at 36°C to 37°C. Pneumatic compression stockings
were placed on the patient. He was maintained on good depth
using oxygen, air, sevoflurane (MAC 0.6-1.2). Fentanyl
infusion was administered at 25mcg/hr. A Fentanyl patch of
25mcg was put on the right arm of the patient. Patient was
maintained on warm intravenous crystalloids such as balanced
salt solution and ringer lactate. 1g MgSO4 was administered as
infusion in 100 ml saline. Throughout surgery patient remained
hemodynamically stable with pulse rate of 84-96/min and
systolic BP of 110-126 mmHg. Urine output was adequate.
Intraoperatively a thickened edematous gall bladder with dense
omental adhesions filled multiple pigment calculi and pus was
noted which was dissected and removed. On completion of
surgery, (duration of 2 hours) neuromuscular block was
reversed with intravenous neostigmine 2.5 mg and
glycopyrrolate 0.4mg. Patient was extubated on table and
shifted to post operative ICU for monitoring with stable
hemodynamics and no pain. He received oxygen supplementation
4-6L/min. Repeated ABG analysis ruled out hypoxia and
acidosis. Patient was hemodynamically stable throughout and
urine output was 100-120ml/hour. Postop period otherwise
uneventful patient kept in propped up and incentive spirometry
re initiated by post op day 2. He was shifted to ward,
discharged on postop day 4.
Discussion
Sickle cell disease must be appreciated as a multi system
disease that affects almost all organs [11]. Vaso-occlusive
phenomena and hemolysis are the clinical hallmarks of SCD, an
inherited disorder due to homozygosity for the abnormal
haemoglobin, that is, HbS. The sickle haemoglobin mutation
results from a single amino acid substitution of valine for
glutamic acid in the 6th position of the beta globin chain
[12]. Homozygous inheritance of sickle cell gene or co
inheritance of the sickle cell gene with another mutataed
haemoglobin variant results in SCD [2,3,12-15]. Vaso-occlusion
results in recurrent painful episodes and a variety of serious
organ system complications which can lead to disabilities and
early death.
Hydroxyurea and other agents have been used to increase the
production of HbF, inhibiting HbS polymerisation [16]. The
hemoglobin (Hb) F molecule does not interact with HbS during
sickling [17]. Thus, the presence of high concentrations of
HbF within the HbS-containing erythrocyte protects this cell
from the distortion, rigidity, and injury incurred during the
sickling process. A result of this is that HbS cells with high
levels of HbF have a survival advantage when compared to HbS
cells containing little HbF [18]. Alkalinisation using
magnesium glutamate, to increase oxygen affinity of Hb in the
RBC has been tried. Oral magnesium supplement reduces
erythrocyte dehydration, reducing the cellular concentration
of HbS in SCD patients [19].
Acute chest syndrome is one of the most serious complications
of SCD. Excessive use of IV fluids as well as respiratory
sedation from the use of opioid medications and adjuvants
potentiate this risk [20]. By definition, acute chest syndrome
is the presence of new pulmonary infiltrates with chest pain,
tachypnoea, hypoxia, dyspnoea, cough, fever or leukocytosis
[11,20,21]. Progressive fibrosis has been detected in children
with multiple episodes of acute chest crisis [22]. It is
difficult to differentiate respiratory symptoms due to
bacterial infection from acute chest syndrome. So, it is
advisable to start patients on broad spectrum antibiotics in
perioperative period. Functional hyposplenism makes these
patients susceptible to streptococcal infection. To prevent
pulmonary complications, prophylactic continuous positive
airway pressures and incentive spirometry should be started
[23].
Proper planning and optimal perioperative preparation is a key
to successful management of SCD patients. Adequate hydration
to decrease the viscosity of blood, control of infections and
getting the haemoglobin levels normal and PCV between 30% and
35% is essential [1]. Normal saline is acidic (9g/dl of sodium
chloride contains 154 milliequivalents of sodium, pH of 5.5,
osmolarity of 308 milliosmoles per litre) and it increases the
viscosity of blood [24]. Hypotonic fluids, in theory, decrease
RBC sickling and are preferred [25-27]. Many of these patients
have impaired kidney function due to renal medulla infarction
which may interfere with their ability to maintain fluid and
electrolyte balance during periods of stress. Preoperative
need for exchange transfusion depends on the general condition
of the patient and the type of surgical procedure. Exchange
transfusion is generally recommended before major surgical
interventions in order to minimise sickling and reduce the
circulating HbS below 30% [28]. In our patient the exchange
transfusions done before surgery reduced the HbS level from
75.3% to 36.7% which drastically improved perioperative
outcome.
Sickle cell disease is a hypercoagulable state [29,30].
Current evidence suggests increased platelet and coagulation
activation, even at patients basal state. SCD patients have
low circulating levels of anticoagulant proteins C and S,
moderate thrombocytosis, decreased platelet thrombospondin 1
content and increased levels of markers of platelet activation
[29,30]. Adequate DVT prophylaxis must be instituted after all
major surgeries until patients are sufficiently ambulatory
[31].
Conclusion
Meticulous anaesthetic management in the form of avoiding
acidosis, hypoxia, hypothermia, hypovolemia, maintaining
normocarbia, good intraoperative and postoperative pain
relief, postoperative thromboprophylaxis, postoperative oxygen
therapy with inspired concentration upto 40%, chest
physiotherapy, nebulisation, incentive spirometry with early
mobilization and regular ABG monitoring played an important
role in improving outcome. Post operative monitoring and pain
relief play an important role in avoiding pulmonary
complications.
Key Points
- Meticulous anaesthetic management is of key importance.
- This is done by avoiding acidosis, hypoxia, hypothermia
and hypovolemia.
- Normal HbF level less than 0.6%.
- Maintaining normocarbia.
- Good intraoperative and postoperative pain relief.
- Postoperative thromboprophylaxis.
- Postoperative oxygen therapy (4L/min).
- Incentive spirometry with early mobilization and regular
ABG monitoring played an important role in improving
outcome.
- Post operative monitoring and pain relief play an
important role in avoiding pulmonary complications.
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