Urinary catecholamines and metabolites in the immediate postoperative period following major surgery
- Correspondence to: Dr A A Syed M4062, Medical Molecular Biology Group, 4th Floor, Cookson Building, Medical School, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK; a.a.syedncl.ac.uk
- Accepted 21 November 2003
Abstract
Background: Induction of anaesthesia can precipitate catecholamine release from an undiscovered pheochromocytoma and induce a hypertensive crisis. However, it is assumed that catecholamine and metabolite values resulting from the effects of surgery per se in the early postoperative period would overlap with the values generated by a tumour, and it is not known how soon after biochemical investigations can be carried out.
Aim: To study patterns of urinary catecholamine excretion and the feasibility of biochemical screening for phaeochromocytomas in the immediate postoperative period in otherwise healthy subjects undergoing a single type of major surgical procedure.
Methods: Catecholamines and metabolites were measured for each mole of creatinine in single voided urine on one preoperative and four postoperative days in five subjects who underwent elective coronary artery bypass graft surgery with an uncomplicated postoperative course. Reference ranges were established from 33 healthy normotensive volunteers.
Results: Excretion of adrenaline, noradrenaline, dopamine, vanillylmandelic acid, and metadrenaline was within normal limits. Normetadrenaline excretion was mildly raised in four patients, but did not exceed 1.5 times the upper reference limit, and returned to normality by the fourth postoperative day.
Conclusion: It is feasible to perform simple urinary screening for possible phaeochromocytoma in the immediate postoperative period.
- A, adrenaline
- DA, dopamine
- MA, metadrenaline
- NA, noradrenaline
- NMA, normetadrenaline
- VMA, vanillylmandelic acid
Although phaeochromocytomas are rare, accounting for 0.1–1% of all cases of hypertension,1 occasionally, unsuspected cases present with a hypertensive episode during the induction of anaesthesia or surgery for unrelated conditions.2,3 It would be reasonable, therefore, to screen for catecholamine secreting tumours in surgical patients in whom hypertension is first seen or becomes difficult to control perioperatively. However, a very high false positive rate in the early postoperative period resulting from the effects of surgery per se is generally expected, and it is not known how soon after surgery biochemical screening tests can be reliably performed. The aim of our study was to determine patterns of urinary catecholamine excretion and the feasibility of biochemical screening for phaeochromocytomas in the immediate postoperative period in otherwise healthy subjects undergoing a single type of major surgical procedure.
MATERIALS AND METHODS
We prospectively studied five subjects (four men) ranging in age from 41 to 75 (mean, 54.8) years who underwent elective coronary artery bypass graft surgery. None of them was administered catecholamines as part of their management and all had a routine postoperative recovery. For the purpose of this preliminary study, we monitored urinary catecholamine and metabolite excretion for each mole of creatinine using “spot” urine specimens, because this eliminates sampling errors of timed collections, and has a sensitivity of 97–100% and a specificity of 98–100%.4–6 Midday self voided or fresh catheter urine was obtained on one preoperative (day 0) and four postoperative days (days 1–4). Thirty three healthy volunteers (14 men, 10 women, nine undeclared sex), ranging in age from 22 to 55 (mean, 35.7) years, with no history of hypertension, served as controls for the determination of reference ranges, and 1.5 times the upper limit was regarded as the threshold of significance.7 Samples were acidified with concentrated hydrochloric acid to pH < 4.0 immediately (within one hour) after collection. Adrenaline (A), noradrenaline (NA), dopamine (DA), metadrenaline (MA), and normetadrenaline (NMA) were measured using high performance liquid chromatography incorporating sample clean up with automated sample trace enrichment of dialysate coupled with electrochemical detection,8 and vanillylmandelic acid (VMA) by gas chromatography of trimethyl silyl derivatives (Pisano reaction).9 Creatinine was measured by a kinetic colorimetric assay (Jaffé reaction).10 A single determination was performed for all analytes. Our study conformed with the ethical principles of the Declaration of Helsinki (Fifth Amendment) and participants gave their consent.
RESULTS
A (reference range, 1–20 nmol/mol creatinine), NA (reference range, 4–185 nmol/mol creatinine), DA (reference range, 83–643 nmol/mol creatinine), MA (reference range, 9–681 μmol/mol creatinine), and VMA (reference range, 0.42–7.27 mmol/mol creatinine) remained well within their respective reference ranges on all days in all subjects (fig 1). Mild increases in NMA (reference range, 5–242 μmol/mol creatinine), not exceeding 1.5 times the upper reference limit, were seen postoperatively in four patients (patients 1–4) on days 1–3, returning to normality by day 4.
Catecholamines and metabolites expressed for each mole of creatinine in single voided urine specimens on one preoperative (day 0) and four postoperative (days 1–4) days in five patients undergoing coronary artery bypass graft surgery. (A) Adrenaline, (B) noradrenaline, (C) dopamine, (D) vanillylmandelic acid, (E) metadrenaline, (F) normetadrenaline (NMA). The solid horizontal lines mark the upper limit of the reference range and the broken horizontal lines (NMA) mark 1.5 times the upper limit. Closed circles, patient 1; open squares, patient 2; open triangles, patient 3; closed squares, patient 4; closed triangles, patient 5; open circles, mean.
DISCUSSION
We report that catecholamine and metabolite excretion is not significantly increased after major surgery using elective open chest coronary revascularisation as an example. We suggest that this is, at least in part, explained by good perioperative anxiolysis and pain relief achieved by modern anaesthetic techniques. This finding reflects a previous report that circulating plasma catecholamine concentrations do not increase significantly above preanaesthetic values in patients undergoing cardiac surgery.11 However, no conclusions could be drawn from urinary measurements in that study because analysis was complicated by the finding of a positive correlation between catecholamine excretion and urine flow rate.
Raised concentrations of NA compared with the hypertensive reference range are often seen in patients with hypertension or myocardial infarction treated with β blockers.12,13 The modest rise in NMA excretion in our study could be a reflection of a similarly raised noradrenergic tone, although NA excretion itself was not increased, and may indicate the need for an “adjusted normal range” for postoperative patients.
“The main advantage of urinary screening in this situation is that it facilitates rapid elimination of phaeochromocytoma from the differential diagnosis”
We acknowledge that urinary screening in surgical patients who experience a stormy perioperative course may be associated with a poor positive predictive value. However, given its very high negative predictive value (100%),14 the main advantage of urinary screening in this situation is that it facilitates rapid elimination of phaeochromocytoma from the differential diagnosis. Although the small number of subjects, who all had a routine postoperative course, limits the applicability of our study, it has established that the general expectation of false positive results in nearly all surgical patients in the immediate postoperative period is erroneous. In conclusion, we propose that it is feasible to investigate patients for possible phaeochromocytoma in the immediate postoperative period by simple urinary screening, but a larger study encompassing a wider spectrum of surgical and anaesthetic procedures is required.
Take home messages
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Catecholamine and metabolite excretion was not significantly increased after major surgery using elective open chest coronary revascularisation as an example
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Therefore, it seems feasible to perform simple urinary screening for possible phaeochromocytoma in the immediate postoperative period, although a larger study encompassing a wider spectrum of surgical and anaesthetic procedures is required
Acknowledgments
We thank all participants in the study and ward staff for their cooperation.
