Skin blood flow and plasma catecholamine concentrations during removal of a phaeochromocytoma in a child

H. Mikasa1, T. Sakuragi*,2, K. Higa1 and M. Yasumoto1

1 Department of Anesthesiology, Fukuoka University School of Medicine, Fukuoka, Japan. 2 Department of Anesthesiology, Chikushi Hospital Fukuoka University, 377-1 Ohaza-Zokumyoin, Chikushino-shi, Fukuoka, 818-8502, Japan

*Corresponding author. E-mail: sakuragi@cis.fukuoka-u.ac.jp

Accepted for publication: January 1, 2004


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 9-yr-old boy with an adrenal phaeochromocytoma underwent removal of the tumour under general anaesthesia using sevoflurane and nitrous oxide combined with thoracic epidural anaesthesia. Skin blood flow in the first toe, as measured by laser Doppler flowmetry, markedly decreased during manipulation of the tumour and increased after removal of it. Skin blood flow correlated more significantly with plasma catecholamine concentrations than did mean arterial blood pressure. Skin blood flow may be used as a non-invasive measure of plasma catecholamine concentrations during removal of a phaeochromocytoma in paediatric patients.

Br J Anaesth 2004; 92: 757–60

Keywords: blood, flow, skin; monitoring; pharmacology, neurotransmitter; surgery, paediatric


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Plasma catecholamine concentrations fluctuate markedly during removal of a phaeochromocytoma. Arterial blood pressure fluctuations are greatest during manipulation of the tumour, and decrease after its removal. However, arterial blood pressure does not always correlate with plasma catecholamine concentrations. Despite increases in plasma catecholamine concentrations, the haemodynamic changes can be minimized by the anaesthetic technique and use of appropriate drugs.1 In search of variables that may correlate with the rapidly changing concentrations of plasma catecholamines, we measured arterial blood pressure, skin blood flow and plasma catecholamine concentrations in a child undergoing removal of a phaeochromocytoma.


    Case report
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A 9-yr-old boy, 115 cm in height and 19 kg in weight, was scheduled for open adrenalectomy. He had a 4-month history of paroxysmal headache and excessive sweating. The arterial blood pressure was 216/164 mm Hg and the heart rate 150 beats min–1 on the first physical examination. A 24-h urinary excretion of catecholamines revealed an epinephrine concentration of 15.2 µg day–1 (normal range, 3–41 µg day–1), norepinephrine 2564 µg day–1 (normal range, 31–160 µg day–1) and dopamine 1782 µg day–1 (normal range, 280–1100 µg day–1). Abdominal computed tomography showed a mass 3 cm in diameter in the left adrenal gland, and 131I-metaiodobenzylguanidine scintigraphy revealed radioactivity only in the left adrenal gland. The patient received prazosin 7.5 mg, propranolol 120 mg and nifedipine 20 mg orally for 2 months before the operation, after which time the arterial blood pressure was controlled at 95/40 mm Hg, and the heart rate to 90 beats min–1. The patient and his parent consented to measurements of skin blood flow and plasma catecholamines during surgery.

The patient was premedicated with oral diazepam 10 mg 2 h before surgery. The arterial blood pressure was 100/60 mm Hg, and the heart rate 130 beats min–1 on arrival in the operating theatre. A peripheral vein was cannulated. Then an epidural catheter was inserted through the T10–11 interspace. T7–T10 analgesia was achieved within 5 min of injection of mepivacaine 1%, 10 ml. Anaesthesia was induced with sevoflurane 8% and nitrous oxide 70% in oxygen. The trachea was intubated after i.v. vecuronium 2 mg. Monitoring included electrocardiography, pulse oximetry, capnography, and radial and pulmonary artery pressure measurements. The patient was placed in a partial right lateral decubitus position. Anaesthesia was maintained with sevoflurane (0.6–1.2%) and nitrous oxide (67%) in oxygen and intermittent epidural injections of mepivacaine 1%. There were no marked changes in the arterial blood pressure or heart rate after starting surgery. However, the arterial blood pressure increased to 200–220/120–136 mm Hg and the heart rate to 106–130 beats min–1 during manipulation of the tumour. The arterial blood pressure was then controlled by an i.v. infusion of sodium nitroprusside 1.5–2.5 µg kg–1 min–1. After removal of the tumour, the arterial blood pressure decreased to 73/41 mm Hg, and sodium nitroprusside was discontinued. The arterial blood pressure stabilized around 100/60 mm Hg after rapid infusion of acetated Ringer solution (500 ml), concentrated red blood cells (400 ml) and albumin (250 ml). Vasopressor was not needed. Surgery lasted 4 h 5 min. Blood loss was estimated to be 475 ml. Anaesthesia lasted 6 h 55 min, during which time a total of 2900 ml of acetated Ringer solution had been infused. The postoperative course was uneventful, and the patient was discharged home on the 17th postoperative day. After surgery, the pathological diagnosis was confirmed to be a phaeochromocytoma.

Plasma catecholamine analysis
Blood samples were taken immediately after the beginning of surgery, during manipulation of the tumour, during ligation of the veins draining the tumour, and after removal of the tumour. Plasma taken during surgery was separated by centrifugation (3000 r.p.m.) at 4°C for 15 min and stored at –80°C for later analysis. Epinephrine and norepinephrine were measured by high-performance liquid chromatography (L-6000TR; Hitachi, Tokyo, Japan) and the trihydroxyindole fluorometric method using a spectrofluorophotometer (RF-5000TR; Shimazu, Kyoto, Japan). The detection limit of this method was 10 pg ml–1for both norepinephrine and epinephrine.

Skin blood flow
This was measured using laser Doppler flowmetry (Advance; ALF-21, Tokyo, Japan). The probe was secured to the left first toe using double-faced adhesive tape. In this method, the beam at a wavelength of 780 nm is delivered from an infrared laser diode to the skin through a flexible optical fibre probe and scattered in a random fashion by moving erythrocytes. The scattered laser beam is captured by light-receiving fibres and directed to the laser flowmetry unit. After conversion of the received light to equivalent electrical signals, signal processing and analysis are performed to obtain the tissue blood flow outputs.

The errors inherent in this method are less than 2 ml 100 g tissue–1 min–1, including those from autocalibration. The laser Doppler flow probe has a fibre separation of 0.7 mm between the exciting and receiving fibres. The optical separation distance can detect blood flow through both capillaries and arteriovenous anastomoses in the outer 1.2 mm of the skin.2 The skin blood flow increased from a control of 32.0 to 40.7 ml 100 g tissue–1 min–1 after epidural anaesthesia. It decreased to 22.9 immediately after manipulation of the tumour and varied from 25.6 to 37.1 ml 100 g tissue–1 min–1 during removal of the tumour. After removal of the tumour, skin blood flow promptly rose from 30.6 to 42.9 ml 100 g tissue–1 min–1, and gradually increased to 49.4 ml 100 g tissue–1 min–1 after surgery. Skin blood flow did not change with body positioning or the infusion of sodium nitroprusside, crystalloids or concentrated red blood cells.

The relationships between plasma norepinephrine concentration and skin blood flow and between plasma norepinephrine concentration and mean arterial pressure are shown in Fig. 1. There was a more significant correlation between plasma norepinephrine concentration and skin blood flow (r = 0.995, P < 0.0001) (Fig. 1A), than between plasma concentration of norepinephrine and mean arterial blood pressure (r = 0.921, P < 0.01) (Fig. 1B). There was also a significant correlation between plasma epinephrine concentration and skin blood flow (r = 0.855, P < 0.05) and between plasma epinephrine concentration and mean arterial blood pressure (r = 0.941, P < 0.01).



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Fig 1 Relationships between (A) plasma norepinephrine concentration and skin blood flow in the first toe, and (B) plasma norepinephrine concentration and mean arterial blood pressure during surgery. Skin blood flow was measured by laser Doppler flowmetry. Blood samples were withdrawn immediately after beginning surgery (a), during manipulation of the tumour (b), during ligation of the draining veins of the tumour (c and d), and after removal of the tumour (e and f).

 

    Discussion
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
During surgery to remove a predominantly norepinephrine-secreting phaeochromocytoma from a child, there were highly significant correlations between plasma catecholamine concentrations, especially norepinephrine, and skin blood flow.

The skin of the fingers and toes contains both capillaries and abundant arteriovenous anastomoses,3 4 the mean diameter of the cutaneous capillaries being 10 µm.2 When constricted, the diameter of the cutaneous arteriovenous anastomoses is also 10 µm, but it increases dramatically to 100 µm when they are maximally dilated, with blood flow increasing up to 10 000-fold.4 The blood flow through the cutaneous arteriovenous anastomoses is regulated by sympathetic nerves that innervate them densely.5 They dilate with the sympathetic blockade of epidural anaesthesia,6 and are constricted by catecholamines.7

Although the skin blood flow in our patient increased after epidural anaesthesia had been established, it decreased and varied in response to manipulation of the tumour. Skin blood flow showed a highly significant correlation with plasma catecholamine concentrations even under epidural anaesthesia, especially the norepinephrine levels. The decrease in skin blood flow in our patient during manipulation of the tumour is therefore thought to have been caused by constriction of the cutaneous arteriovenous anastomoses from the increased levels of catecholamines released from the tumour. The results also show that skin blood flow can be used as a non-invasive measure of rapidly changing plasma catecholamine concentrations in children with a phaeochromocytoma.

In conclusion, this case shows that there are significant negative correlations between plasma catecholamine concentrations and skin blood flow in a child with a phaeochromocytoma, demonstrating that skin blood flow may be used as a non-invasive and real-time indicator of plasma catecholamine concentration in such circumstances. This technique may assist the surgeon who is uncertain whether a phaeochromocytoma has been completely isolated from the systemic circulation.


    References
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
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4 Rubinstein EH, Sessler DI. Skin-surface temperature gradients correlate with fingertip blood flow in humans. Anesthesiology 1990; 73: 541–5[ISI][Medline]

5 Iijima T, Tagawa T. Adrenergic and cholinergic innervation of the arteriovenous anastomosis in the rabbit’s ear. Anat Rec 1976; 185: 373–9[ISI][Medline]

6 Mori A, Sakuragi T, Horie T, Dan K. Inhibition by sedatives of compensatory vasoconstriction during lumbar epidural anesthesia. Masui 1994; 43: 195–200[Medline]

7 Sherman JL. Normal arteriovenous anastomoses. Medicine 42; 1963: 247–67