Anaesthesia, 1986, Volume 41, pages 1225-1229

CASE REPORT

Vecuronium and phaeochromocytorna

A report of two cases using different modes of administration

M . J . D A R O W S K I , W . B. A . C O U T I N H O , S . J . P O W E R AND R. M . JONES

Summary
Two patients presenting for removal of phaeochromocytoma are described. Vecuronium was used to provide
neurornuscular blockade by two different methods of administration: an infusion and a large bolus dose.
Both gave satisfactory results and we suggest that vecuroniurn may be the neuromuscular blocking agent
of choice for patients uith phaeochromocytoma.

Key words
Neurornuscular relaxants; vecuronium.
Surgery; phaeochromocytoma.

Vecuronium has been shown t o be remarkably
cardiostable’ - 4 and to cause minimal histamine
release.’ These properties suggest that it may be
the muscle relaxant of choice for patients with
phaeochromocytoma.6 We report the details of
two patients in whom vecuronium was admin-
istered by different modes in order to achieve
muscle relaxation during anaesthesia for phaeo-
chromocytoma removal.
Case histories
Case 1
A 37-year-old male weighing 69 kg presented for
removal of phaeochromocytorna. He had a 2-year
history of hypertension which had been
diagnosed during an admission to hospital for a
nasal operation. He had a hypertensive reaction
and marked cardiac dysrhythmias during anaes-
thesia on that occasion. The acute episode was
treated with intravenous practolol and he was
discharged to the care of his general practitioner
who treated his hypertension with a /3-adrenergic
antagonist which was later changed t o spiro-
nolactone.
Earlier in the year he presented again for minor
surgery t o a toe. His arterial blood pressure was
180/120 mmHg. He was premedicated with
papaveretum 15 mg and hyoscine 0.3 mg one
hour pre-operatively and was noted to be anxious
on arrival in the anaesthetic room. Anaesthesia
was induced with thiopentone; he then developed
severe hypertension (systolic arterial pressure
200 mmHg) and a tachycardia of 140 beats/
minute. This eventually responded to an infusion
of sodium nitroprusside and a bolus of practolol.
A preliminary diagnosis of phaeochromocytoma

M.J. Darowski. MB. ChB, FFARCS. Senior Registrar, Department of Anaesthetics, Guy’s Hospital, St Thomas’s
Street, London SEI 9RT, W.B.A. Coutinho, MB, BS, FFARCSI, FFARCS, Senior Registrar, Department of
Anaesthetics, Greenwich District Hospital, Vanbrugh Hill, London SElO 9HE. S.J. Power, MB, BS, FFARCS,
Lecturer in Anaesthetics. R.M. Jones, MB, ChB, FFARCS, Senior Lecturer in Anaesthetics, The United Medical
and Dental Schools ofGuy’s and St Thomas’s Hospitals (University of London), Guy’s Hospital, London SEI 9RT.

0003-2409/86/121225 + 05 W3.00/0@ 1986 The Association of Anaesthetists of Gt Britain and Ireland 1225
1226 M.J. Darowski et al.
was made and this was confirmed following
estimation of urinary catecholamine metabolites.
He was started on labetolol 100 mg twice daily.
A postoperative ECG showed ST elevation and
T-wave inversion in leads V2-,.
He was transferred to this hospital for definitive
treatment. He gave a 2-year history of episodes
of palpitations, sweating, headaches and anxiety
attacks, which occurred 1-2 times a month and
were often brought on by straining at stool.
Physical examination was normal, apart from
an arterial blood pressure of 170/100 mmHg.
Serum and urinary catecholamine levels were
markedly raised. A random blood sugar was
6.3 mmol/litre (normal range 3.3-5.5 mmol/litre).
Other blood results were normal. The ECG
showed evidence of a small anteroseptal infarct
with subendocardial extension. This had most
probably occurred during his last anaesthetic.
'
Computerised tomography and an I '-labelled
meta-iodo-benzyl-guanidine (MIBG)' scan
showed a solitary phaeochromocytoma in the
region of the left adrenal.
Adequate control of his blood pressure was
achieved following 40 days incremental treatment
with phenoxybenzamine 90 mg tds, propranolol
60 mg tds and a-methyl-para-tyrosine* 500 mg
three times a day. When his arterial blood
pressure had fallen to 120/8&130/90 mmHg, he
was prepared for surgery. He was alert and
complained of feeling restless and agitated.
He was premedicated with papaveretum 20 mg
and hyoscine 0.4 mg one hour pre-operatively
and arrived in the anaesthetic room very sedated.
ECG leads and an automatic blood pressure cuff
(Accutor Datascope) were placed and baseline
readings obtained. Anaesthesia was induced with
nitrous oxide in 30% oxygen and isoflurane up
to 2%. An intravenous line and a radial artery
cannula were sited and a continuous display of
arterial blood pressure obtained. Electrodes for
the neuromuscular transmission monitor (Datex
Relaxograph) were placed over the left ulnar
nerve and hypothenar eminence and calibration
and baseline values were obtained. Fentanyl 1.5
pg/kg and vecuronium 28 mg (0.4 mg/kg, EDpl x
8) were given into a fast-running infusion. Neuro-
muscular blockade was monitored by train-of-
four (TOF) stimulation every 20 seconds.
Ventilation of the lungs was assisted at the
onset of paralysis, laryngoscopy performed and
the larynx sprayed with 4% lignocaine. The
trachea was intubated within 90 seconds of
administration of the vecuronium. There was no
increase in either heart rate or arterial blood
pressure in response to either relaxant admini-
stration, laryngoscopy or tracheal intubation. A
central venous catheter was sited via the right
internal jugular vein and the bladder was cath-
eterised. Anaesthesia was maintained with
nitrous oxide in 30% oxygen with isoflurane
0.5-1 YO.The patient was gently turned to the
right lateral position and surgery allowed to
proceed. Neither position nor surgical incision
produced responses in either heart rate or arter-
ial blood pressure.
Dissection and manipulation of the tumour
initiated a rise in arterial blood pressure to a peak
of 182/117 mmHg which was treated first by
increasing the isoflurane concentration to 2%,
then by increments of phentolamine 1 mg to a
total of 7 mg and finally by a brief infusion of
sodium nitroprusside. The arterial blood pressure
settled to a systolic of 100 mmHg over a period
of 15 minutes. No dysrhythmias were seen. The
arterial blood pressure decreased rapidly to 80
mmHg systolic after removal of the tumour and
2 mg methoxamine were administered to return
it to 100 mmHg. Blood loss was 350 ml. The
remainder of the operative course was uneventful
and no further increments of analgesia or muscle
relaxant were required.
TIhad returned to 20% of control at the end
of the procedure, one hour and 55 minutes after
the injection of vecuronium. Neuromuscular
blockade was reversed with edrophonium 0.5
mg/kg and glycopyrrolate 0.005 mg/kg. Reversal
was prompt with a return of T , to 50% of control
and a Tq ratio of 0.5 within a minute. The
isoflurane was switched off and the trachea
extubated once spontaneous ventilation was
established.
The patient remained very drowsy in the post-
operative period, and was still not fully awake
some 12 hours postoperatively, despite a normal
blood sugar level.g Large volumes of colloid were
required to maintain central venous pressure,
arterial blood pressure and urine output in the
first 24 hours and the patient required 3 litres of
plasma and 2 units of blood. He developed a
staphylococcal pneumonia within the first 14
postoperative hours for which he required con-
trolled ventilation of the lungs for 30 hours. He
responded well to physiotherapy and a course of
cephazolin and his further postoperative course
was uneventful.

Case 2
A 30-year-old female presented for removal of
phaeochromocytoma. She was discovered to be
hypertensive earlier in the year, when she visited
her general practitioner to be prescribed the oral
contraceptive pill. Her only complaint was of
occasional episodes of palpitations and in the
CQUrSe of investigation she was found to have
raised levels of vanillylmandelic acid. She had
had uneventful general anaesthesia in both 1980
and 1983 and was noted to be normotensive on
both occasions. Her general practitioner had
started treating her with nifedipine slow release
20 mg twice daily.
On admission, her arterial blood pressure was
220/120 mmHg. Her physical examination was
otherwise normal. She gave a one-year history of
attacks of palpitations. She was taking no
medication apart from nifedipine. She had raised
urinary and serum catecholamine levels and
mildly raised thyroid function tests. An
MIBG scan showed an area of massive uptake
above the left kidney. Her ECG showed sinus
tachycardia.
Her blood pressure after admission stabilised
at 110/70 mmHg after 3 weeks treatment with
phenoxybenzamine 30 mg, propranolol 20 mg
and nifedipine 20 mg all twice daily and Lugol's
iodine (10 drops/day) for six days.
She was premedicated with lorazepam 2 mg
otally 2 hours pre-operatively, followed by
papaveretum 15 mg and hyoscine 0.3 mg an hour
later. On arrival in the anaesthetic room fentanyl
100 pg was given by slow intravenous injection
through an indwelling needle. A radial artery
cannula, an intravenous cannula and a right atrial
cannula via the right internal jugular vein were
all sited under local anaesthesia. Electrodes for
the neuromuscular transmission monitor (Datex
Relaxograph) were placed as described pre-
viously. Anaesthesia was induced with thiopen-
tone 250 mg followed by a further 150pgfentanyl.
Ventilation was assisted by facemask, while
calibration and baseline recordings of neuro-
muscular function were obtained. Vecuronium
5 mg was administered and, after an interval of
2 minutes, the trachea was intubated. There was
no rise in heart rate or blood pressure following
either induction of anaesthesia, relaxant admin-
istration or intubation of the trachea. Anaesthesia
was maintained with nitrous oxide in 33% oxygen
and isoflurane 0.5-1%. Ventilation of the lungs
Vecuronium and phaeochromocytoma 1227
was controlled to maintain normocarbia (Datex
capnograph). Neuromuscular function was mon-
itored by train-of-four every 20 seconds. When
twitch height had returned to 10% of control an
infusion of vecuronium (0.2 mg/ml) was started.*O
The infusion was delivered by a Vickers Treonic
syringe pump and adjusted to maintain a twitch
height between loo/, and 15% of control.
Surgical incision and abdominal exploration
produced a rise in blood pressure to a peak of
200 mmHg systolic. This was treated with incre-
ments of phentolamine 1 mg (total 5 me). Blood
pressure settled to control within minutes of
removal of the tumour. There were no dysrhy-
thmias. Blood loss was approximately 500 ml.
The vecuronium infusion was stopped towards
the end of the procedure and at the end of surgery
T I had reached 50% of control. Residual
neuromuscular blockade was reversed with
neostigmine 2.5 mg and glycopyrrolate 0.5 mg.
A T4 ratio of 0.5 was achieved within a minute
of reversal. Anaesthesia had lasted for 90 minutes
and 1.8 mg of the vecuronium infusion had been
administered. When spontaneous ventilation was
established, the trachea was extubated and the
patient transferred to the intensive care unit
where she made an uneventful recovery.
Discussion
The mortality due to surgery for removal of
phaeochromocytoma has declined dramatically
over the past three A number of
factors have probably contributed to this
d e ~ l i n e , ' ~ .although
'~ the precise role of im-
proved anaesthetic technique is difficult to
quantify." There is, however, no doubt that the
choice of anaesthetic agent@) can, and does,
influence the incidence of intra-operative
complications such as hypertension and dysrhy-
thmia.14*16
All muscle relaxants, with the possible excep-
tion of vecuronium, have the potential to cause
cardiovascular side effects which may, or may
not, be associated with histamine release. In
patients with phaeochromocytoma, histamine
release is particularly undesirable because it can
cause hypertension and indeed, this has been
used as a diagnostic test for the condition."
Vecuronium probably has the least tendency to
cause histamine release3.' * of all the available
relaxants. Suxamethonium is relatively contra-
indicated in patients with phaeochromocytoma,
1228 M.J. Darowski et al.
both because of its autonomic side effectsl9-21
and also because fasciculations may cause release
of catecholamines from the tumour.l6 Pancuron-
ium has little potential to initiate histamine
r e l e a ~ e ,but
~ it has been reported to cause
hypertension in a patient with phaeochromocy-
toma,” presumably due to its sympathomimetic
a~tivity.’~.’‘ Similarly, gallamine has sym-
pathetic activity which, coupled with a marked
tachycardia due to vagal blockade, means this
agent is unsuitable.”
Theoretically, therefore, vecuronium appears
to be the agent of choice for patients with
phaeochromocytoma and its successful use in this
situation has been reported.6 The customary
method of administration by intermittent bolus
doses has the disadvantage that it results in
fluctuating levels of muscle relaxation. This may
be particularly undesirable in patients with
phaeochromocytoma, in whom coughing and
straining may cause sudden massive catechola-
mine
Administration by infusion has been suggested
as an answer to this problem and in our report
this technique worked satisfactorily. However,
the use of infusions of muscle relaxant necessitates pre-operatively. It was interesting that he was
the availability of a method of reliable delivery
of the drug and of monitors of effect; without
these, the technique cannot be used.
An alternative is the use of a large bolus dose
of vecuronium which prolongs its duration of
action. We administered an ED95 x 8 dose
(28 mg) of vecuronium and have demonstrated
that even this very large bolus did not cause any
cardiovascular effects and provided satisfactory
relaxation for the entire procedure.
The use of isoflurane for anaesthesia in patients
with phaeochromocytoma has been well docu-
mented.26-Z*Previous authors have commented
on the stability of cardiac rhythm during iso-
flurane anaesthesia for removal of catecholamine-
secreting turnours. Neither of our patients had
any disturbances of cardiac rhythm, other than
sinus tachycardia, at any time. This included, in
both patients, the period of tumour manipulation,
when the sudden increase in arterial pressure
(despite adequate pre-operative a- and /I- surgical relaxation. In our patient, even this very
blockade) suggests that circulating catecholamine
levels must have been substantially increased. A
further advantage of isoflurane is that it is a
potent vasodilator, and because of its low
blood/gas partition coefficient, rapidly reversible presenting for the removal of a phaeochromo-
changes in systemic vascular resistance and thus
in arterial blood pressure can be attained. In
a sense it may be termed ‘inhalational sodium
nitroprusside’.
The patient in Case 1 had required treatment
with a-methyl-para-tyr~sine***~ to control his
hypertension: This is a competitive inhibitor of
tyrosine hydroxylase which acts centrally as well
as in the periphery. This enzyme is the rate-
limiting step in catecholamine synthesis. In
patients with phaeochromocytoma, treatment
reduces daily catecholamine synthesis by 20-80%.
Either on its own, or in combination with
phenoxybenzamine it usually produces adequate
control of blood pressure and of symptoms and
has been used for the treatment of patients with
malignant phaeochromocytoma not amenable to
surgical
Alpha-methyl-para-tyrosine has two side
effects of anaesthetic importance. First, it can
potentiate the extrapyramidal side effects of
butyrophenones (e.g. droperidol) and second it
may cause sedation, which will potentiate the
effects of other central nervous system depres-
sants. Occasionally, psychic stimulation may
occur and our patient was restless and agitated
very heavily sedated following premedication,
even though similar premedication with his
previous anaesthetic had been described as
inadequate. Phenoxybenzamine is also reported
to cause sedation,” so that the precise nature of
the interaction is difficult to interpret. Whatever
the cause, it seems likely that his prolonged period
of peri-operative sedation and hence relative
immobility was a contributory factor to his
postoperative pulmonary complications.
In summary, we have described two techniques
for administering vecuronium to patients anaes-
thetised for removal of phaeochromocytoma.
Both were very satisfactory in the cases described
and the choice of technique may be influenced
by the availability of infusion devices and of
methods of monitoring neuromuscular trans-
mission. If such devices are not available, we
suggest that the use of a large bolus dose
(0.4 mg/kg, EDss x 8) will produce prolonged
large dose of vecuronium was without cardio-
vascular side effects. We suggest that whatever
the method of administration, vecuronium is
probably the muscle relaxant of choice in patients
cytoma.

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