Abstract
Methemoglobinemia is a rare but serious haemoglobin disorder
when red blood cells contain methaemoglobin at levels higher
than 1%. Basically, it results from the oxidation of the
ferrous iron in haemoglobin to the ferric iron. Methaemoglobin
is incapable of carrying O
2, and high levels can
impair O
2 delivery to the tissues.
Methemoglobinemia can be congenital or acquired. Acquired
methemoglobinemia is more common than the congenital variety.
Several factors must be considered when anesthetizing patients
with methemoglobinemia, which include the potential for
decreased oxygen delivery, which may be exacerbated by
intraoperative blood loss and anaemia, interference with
normal intraoperative monitoring devices, and the potential
for medications to cause or exacerbate methemoglobinemia.
Here we describe a patient with congenital methemoglobinemia,
which was diagnosed during preop evaluation for renal
transplant on the basis of a discrepancy between the O
2
saturation noted by pulse oximetry and that obtained from
arterial blood gas analysis and found to have NADH cytochrome
b5 reductase deficiency. He is now posted for
parathyroidectomy and total thyroidectomy. Anaesthetic care of
patients with methemoglobinemia is discussed with a brief
review on the topic.
Key words: Methemoglobinemia, Thyroidectomy,
Oxygen delivery. Oxygen saturation- interpretation.
Introduction
Methemoglobinemia is a condition with a life-threatening
potential in which a reduction in the oxygen-carrying capacity
of circulating haemoglobin occurs due to conversion of some or
all of the four iron species from the reduced ferrous [Fe
2+]
state to the oxidized ferric [Fe
3+] state. Ferric
iron is unable to bind and transport oxygen. So Increased
levels of methaemoglobin results in a state of functional
anaemia.
Methemoglobinemia may result from congenital or acquired
causes. Congenital forms of methemoglobinemia are due to
autosomal recessive defects in the enzyme cytochrome b5
reductase (CYB5R) or due to autosomal dominant mutations in
the genes that code for globin proteins collectively known as
haemoglobins M [1]. Acquired methemoglobinemia, is much more
common, is the result of exposure to substances that cause
oxidation of the haemoglobin either directly or indirectly.
This exposure results in the production of methaemoglobin that
exceeds the body's capacity to convert the iron within the
haemoglobin back to its ferrous state. Acquired
methemoglobinemia may be due to exposure to direct oxidizing
agents (e.g., benzocaine and prilocaine), indirect oxidation
(e.g., nitrates), or metabolic activation (e.g., aniline and
dapsone) [2]
We report a patient with diagnosed congenital
methemoglobinemia undergoing parathyroidectomy and total
thyroidectomy. The pathophysiology, aetiology, clinical
manifestations, anaesthetic considerations, and treatment
options of methemoglobinemia are discussed.
Case report
A middle aged male, known case of diabetes, hypertension,
coronary artery disease, post renal transplant presented to
hospital with swelling infront of neck of one year duration.
He was found to have hyperparathyroidism also.
Ultrasonography of neck showed TR 1/2/3 nodule of both
thyroids and 7.7 x 6 mm lesion right hemi thyroid. Parathyroid
hormone (PTH) level was found to be high. MIBI scan showed
parathyroid adenoma. So he was planned to undergo
parathyroidectomy and total thyroidectomy by endocrine
surgeons.
Percutaneous transluminal coronary angioplasty had been done
twice a few years back. He developed chronic kidney disease
and underwent a successful renal transplant couple of years
back. He was diagnosed to have methemoglobinemia due to NADH
cytochrome b5 reductase deficiency at the time renal
transplant.
He had poor effort tolerance of less than 4 METS. The physical
findings were unremarkable, except for mildly cyanotic lips
and nails. Vitals were pulse rate of 60 beats/min, regular and
blood pressure of 160/90mm Hg in the right arm in sitting
position. Patient's initial pulse oximetry reading was 91% on
room air. On assessment of the airway, mouth opening was
normal with adequate neck movements and Mallampati grade was
2. Neck examination revealed grade 2 goitre without
compressive features or retrosternal extension. He had no
features of hypo or hyperthyroidism.
His blood investigations were - Hb 17.7gm%, platelet
count - 1.65 lakhs/mm
3, total count 6900 cells/mm
3,
packed cell volume 57.2%, serum creatinine 1.25 mg/dl, serum
sodium 137 meq/L, serum potassium 4.2 meq/L, random glucose
159 mg/dl, total thyroxine/T 4 7.51 ug/dl, TSH
0.823uIU/ml, PTH 251, serum calcium 10.1, phosphorous 3.
Methemoglobin work up showed methemoglobin level 9.8%
(normal < 2%) and NADH-cytochrome b5 reductase level
15.59 IU/gHb (normal value 30-40). Chest X-ray showed
cardiomegaly and electrocardiogram showed T wave inversion in
I, aVL, V5, V6 leads. Echo showed concentric left ventricular
hypertrophy, regional wall motion abnormality and grade 2 left
ventricular diastolic dysfunction.
Cardiology, Nephrology and Haematologist opinions were
obtained before taking for surgery. Written informed high-risk
consent was taken before surgery in view of CAD, CKD,
methemoglobinemia and patient kept fasting for 6-8 hours.
On the day of surgery, In the premedication room, a
chocolate-brown coloured blood was noted while cannulating the
vein. He received injection midazolam 1mg, 0.2mg
glycopyrrolate, 8 mg dexamethasone, 4mg ondansetron and
antibiotic under supervision and monitoring.
In the operation theatre, all standard ASA monitors - 5 lead
ECG, non-invasive blood pressure and pulse oximeter were
attached. Room air saturation was 90%. Preoxygenation was done
with 100% oxygen for 5 minutes. Saturation was increased to
100%. He was given fentanyl 100 mcg, priming done with
atracurium and induced with etomidate 16 mg. Induction was
performed with care to avoid hypotension and hypoxia.
Atracurium 40 mg was given and intubated with 8 mm ID cuffed
NIM FLEX endotracheal tube (nerve integrity monitoring
Endotracheal tube) with cuff pressure of 25 cm H
2O
and fixed it after bilateral air entry was confirmed.
Maintenance was done with oxygen, air, sevoflurane and
fentanyl 50 mcg/hr ensuring adequate depth of anaesthesia
using entropy value of 40-60. Further administration of muscle
relaxant was avoided because it will interfere with myographic
signal with nerve integrity monitoring. An arterial line was
inserted in the left radial artery. Intraoperatively, 1 Gram
Paracetamol was given as infusion. We avoided NSAIDs and all
drugs which will may precipitate methemoglobinemia like
lidocaine, eutectic mixture of local anaesthetics cream,
nitrous oxide, metoclopramide, nitroglycerine, sodium
nitroprusside [3,4]. Adequate hydration was given with
crystalloids ringer lactate and balanced salt solution
(Sterofundin). Patient was positioned in a slight head up and
neck extended position.
Patient was mechanically ventilated in a PCV-VG mode and the
ventilatory settings were adjusted to end tidal carbon dioxide
monitoring and care given particularly to avoid hypoxia. The
temperature was monitored using a probe and maintained at 35◦C
to 36◦C. Intermittent pneumatic compression device for
thromboprophylaxis was placed. Intraoperatively patient was
hemodynamically stable throughout the procedure. Once the
surgery was over, neuromuscular blockade was reversed with 3
mg of neostigmine and 0.6 mg glycopyrrolate intravenously. He
was extubated and then shifted to post operative ICU. Patient
was kept in a slight propped up position and oxygen were
supplemented at 4-6L/min via Hudson facemask.
Discussion
Methaemoglobin forms when haemoglobins Fe ion oxides from
ferrous (Fe
2+) to ferric (Fe
3+). In
healthy adults, a small amount of haemoglobin oxides to
methaemoglobin and then it is rapidly converted back to
haemoglobin such that methaemoglobin levels remain below 1%
[5]. Methemoglobinemia is a rare but serious haemoglobin
disorder when red blood cells contain methaemoglobin at levels
higher than 1% [5].
Symptoms of methemoglobinemia appear depending on
methaemoglobin level in blood. Chocolate colour cyanosis
presents at levels of 5-15% and appears early in anaemic
patients. At 30-40%, weakness, headache, dyspnoea, tachycardia
and dizziness occurs. Patient will be lethargic, stuporous,
confused and comatose at concentration of 55-60%. At 70%,
circulatory collapse occurs [3,4].
Methemoglobinemia may result from congenital or acquired
causes. Congenital forms of methemoglobinemia are due to
autosomal recessive defects in the enzyme cytochrome b5
reductase (CYB5R) or due to autosomal dominant mutations in
the genes that code for globin proteins collectively known as
haemoglobin M [1]. Acquired methemoglobinemia is usually due
to the exposure of drugs or chemical substances such as amyl
nitrite, ethyl nitrite, sodium nitrite, silver nitrate,
bismuth subnitrate, nitro-glycerine, quinones, dapsone,
sulphonamide, sulphapyridine, sulfathiazole, aniline dye,
acetanilid, aminobenzenes, aminophenol, benzocaine,
prilocaine, and phenacetin [3,6]. The drugs used in
anaesthetic practice that has the potential to cause
methemoglobinemia are prilocaine, benzocaine, amyl nitrite,
nitroglycerine, phenacetin, and sulphonamide.
Methaemoglobin has the same absorbability as Oxyhaemoglobin
and Deoxyhaemoglobin so can affect oxygen saturation
measurements by the pulse oximeter [7]. Therefore, the pulse
oximeter cannot monitor methaemoglobin levels. Arterial blood
gas analysis calculates oxygen saturation based on arterial
oxygen tension and the temperature and may not reflect actual
oxygen saturation. Methemoglobinemia diagnosis includes
cyanosis; low arterial oxygen saturation that cannot be
explained by a problem in the respiratory system or
cardiovascular system; and when the normal oxygen partial
pressure in the arterial blood gas analysis does not align
with the oxygen saturation by the pulse oximeter. Oxygen
carrying status is most accurately measured by analysis of all
haemoglobin types with a co-oximeter [8].
Intraoperative monitoring should ideally include co-oximetry,
which detects the presence as well as quantifies
methaemoglobin level [9]. Pre-operative treatment with vitamin
C helps in non-enzymatic reduction of methaemoglobin.
Injection methylene blue is the antidote and the dose is 1-2
mg/kg IV over 3-5 min [10,11]. It acts by increasing the level
of NADH methaemoglobin reductase, which helps in conversion of
ferric ion to ferrous ion [12]. Exchange transfusion and
haemodialysis is indicated in severe cases. In acquired
methemoglobinemia offending drug should be withdrawn and care
should be taken to avoid further exposure to the offending
agent.
Conclusion
In conclusion avoidance of exposure to oxidizing agents is
important in patients with congenital methemoglobinemia
because of their deficient enzymatic pathways and decreased
oxygen-carrying capacity. Preoperative considerations for
congenital methemoglobinemia include the supplementation of
oxygen of higher concentration, examination of methaemoglobin
by co-oximetry to determine whether the oxygenation is
adequate, avoidance of the use of oxidizing drugs (such as
lidocaine, benzocaine, prilocaine, nitroglycerine), and
treatment with methylene blue if methemoglobinemia
deteriorates severely. If the patient is not responsive,
exchange transfusion should be considered. To deliver safe
anaesthesia in patients with congenital methemoglobinemia, it
is important to recognize the nature of this rare disease, and
to know how to correctly treat the patient who has sustained
oxygen desaturation.
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