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Acta Anaesthesiol Scand 2008; 52: 487–492 r 2008 The Authors Printed in Singapore. All rights reserved Journal compilation r 2008 The Acta Anaesthesiologica Scandinavica Foundation ACTA ANAESTHESIOLOGICA SCANDINAVICA doi: 10.1111/j.1399-6576.2007.01551.x Perioperative concentrations of catecholamines in the cerebrospinal fluid and plasma during spinal anesthesia 1,2 3 4 5 2 2 M. J. OEHMKE ,T.PODRANSKI ,M.MANN ,N.FRICKEY ,D.F.M.KUHN and G. HEMPELMANN 1Department of Special Anaesthesia and Pain Control, Medical University of Vienna, Vienna, Austria, 2Department of Anaesthesiology, Intensive Care Medicine, Pain Therapy, University Hospital Giessen, Giessen, Germany, 3Outcomes Research Consortium, The Cleveland Clinic, Cleveland, OH, USA, 4Institute of Medical Informatics, Working Group Medical Statistics, University of Giessen, Giessen, Germany, 5Department of Anaesthesia, General Intensive Care, and Pain Control, Medical University of Vienna, Vienna, Austria Background: Catecholamine release is a physiological re- [249;422] to 556 [423;649] pmol/l and remained elevated sponse to stress. The extent to which perioperative stress 24 h after surgery (P 5 0.009). There was no association provokes the central release of catecholamines, which modu- between changes in CSF or plasma norepinephrine or late pain perception in the spinal cord, still remains unknown. epinephrine concentrations and changes in heart rate The perioperative course of catecholamine concentrations in (HR) or mean arterial pressure (MAP). the cerebrospinal fluid (CSF) and plasma was examined. Conclusion: During spinal anesthesia for elective hip joint Methods: Aprospectivestudywasperformedin25pa- replacement, norepinephrine concentrations were greater tients (ASA III, 60–84 years) undergoing elective hip joint in plasma than in CSF. CSF dopamine and epinephrine replacement in spinal catheter anesthesia. The concentra- concentrations were essentially undetectable. The changes tions of dopamine, epinephrine and norepinephrine in the in CSF-norepinephrine concentrations and the changes of CSF and plasma were measured before anesthesia, imme- plasma norepinephrine concentrations showed no associa- diately after surgery, and 6 and 24 h post-operatively. tion with each other; nor were there correlations between Results: In most patients, dopamine and epinephrine clinical stress parameters (HR, MAP) or visual analog scale were not detectable in CSF. CSF–norepinephrine concen- pain, and the changes in CSF norepinephrine concentra- trations decreased from median [interquartile-range] tions. 159 [124;216] pre-anesthesia to 116 [79;152] pmol/l imme- diately post-operatively and were slightly elevated 24 h post-operatively (180 [134;302] pmol/l) (P 5 0.05). Dopa- Accepted for publication 14 October 2007 mine plasma concentrations were not detectable or were Key words: Catecholamines; cerebrospinal fluid; plasma; barely above the detection threshold. Plasma epinephrine perioperative; epinephrine; norepinephrine; dopamine; increased from 61 [28;77] pmol/l pre-anesthesia to 112 concentration. [69;138] pmol/l 6 h post-operatively and returned to base- line 24 h post-operatively (P 5 0.001). Plasma norepinephr- r 2008 The Authors ine concentrations increased intra-operatively from 298 Journal compilation r 2008 The Acta Anaesthesiologica Scandinavica Foundation NTICIPATION of surgery, even with general an- response to surgical stress, the extent to which Aesthesia, triggers physical and psychological surgical stress provokes the central release of ca- stress in patients (1, 2). This results in an endocrine techolamines remains unknown. Because catecho- response mediated by the hypothalamic–pituitary– lamines modulate pain perception in the spinal adrenal and renin–angiotensin axes, along with cord (10–14), and differences in catecholamine sympathetic nervous system activation (3). levels may affect analgesia, we chose to investigate The most basic physiological response to stress, the catecholamine concentrations in the cerebrosp- including that resulting from surgical tissue injury, inal fluid (CSF). is release of catecholamines (4–7). The major cate- Therefore, this study determined the periopera- cholamines, dopamine, epinephrine, and norepi- tive changes of catecholamine concentrations in the nephrine are released both peripherally and CSF and plasma in elderly patients undergoing centrally (8, 9). major hip surgery. Possible correlations between While it is well established that peripheral cate- CSF and plasma catecholamine concentrations, cholamine concentrations increase markedly in heart rate (HR), mean arterial pressure (MAP), 487 M. J. Oehmke et al. and the visual analog scale (VAS) pain score were Germany), an indirect sympathomimetic agent, analyzed. and the study was discontinued. During anesthesia, patients received midazolam as required in steps of 1 mg i.v. up to a maximum Methods of 6 mg. Patients also received 3 l/min O2 via a nasal tube, volume substitution, and monitoring With the approval of the local Ethics Committee of SaO2. Post-operatively, patients received single and written informed patient consent, 25 patients dosages of 2 mg morphine i.v., as requested, if were enrolled in this prospective study. Inclusion pain was rated 43 on a 10-cm-long VAS with criteria were an age of 60 years or above with ASA each centimeter marked and numbered 0–10, Physical Status III undergoing elective total hip where 0 cm indicates no pain and 10 cm the worst joint replacement with spinal-catheter anesthesia. possible pain. The surgeon used cemented MS-30 stems and All values recorded for statistical analysis (HR, polyethylene screw-in cups (Biomet Deutschland MAP, VAS, and catecholamine concentrations) GmbH, Berlin, Germany). Exclusion criteria were were sampled at the measurement points immedi- decompensated cardiac or circulatory insufficiency, ately before administration of the local anesthetic severe renal or hepatic impairment, signs of clot- (pre-LA), immediately postoperative (0 h post-OP), ting disorders, neuromuscular dysfunction, dis- 6 h post-operatively (6 h post-OP), and 24 h post- eases of endocrine organs (diabetes, pancreatitis, operatively (24 h post-OP). Five milliliters of CSF thyroid problems, hepatitis), known tumors/neo- from the spinal catheter and an equal volume of plasmas, alcohol or drug abuse, use of substances blood from a central-venous catheter were ob- acting on the central nervous system, and use of tained in pre-chilled tubes and placed on ice at all calcium antagonists, a2- and b-sympathomimetics, measurement points. For storage purposes, fluid or theophylline. samples were centrifuged (10 min, 4000 U/min, One hour before surgery, 3.75 mg oral midazo- 4 1C) within 15 min and the supernatant frozen lam (Dormicum, Hoffmann-La Roche AG, Basel, at À 20 1C. Switzerland) was administered. During the pre- The concentrations of dopamine, epinephrine, paration for anesthesia, a 16 G central venous and norepinephrine in the CSF and plasma were line (Cavafix Certodyn 375, B. Braun, Melsungen, determined in a single batch for each parameter Germany) was placed in the basilic vein and by means of high-performance liquid chromato- correct placement checked by ECG. A 20 G graphy (HPLC) with electrochemical detection arterial line (B.Braun) was inserted into the radial (Reagent Kit Catecholamines in Plasma, Chromsys- artery. tems Instruments & Chemicals GmbH, Mu¨ nchen, HR from the ECG and MAP were recorded at Germany) (15). The lower limits of detection were 5-min intervals until the end of surgery, and then 1, 20 pmol/l or less. The intra-assay coefficients of 3, 6, 12, and 24 h post-operatively. For anesthesia variation were 5.6% for dopamine, 4.9% for epi- and sampling, a 20 G spinal catheter (Perifix, B. nephrine, and 2.8% for norepinephrine. Glucose Braun) was placed at L2/3 or L3/4. Anesthesia was was measured by photometry (Test-Combination initiated with 2.5 ml of isobaric bupivacainhy- Glucoquant Glukose, Boehringer, Mannheim, Ger- drochloride 0.5% (Carbostesin 0.5%, Astra, Ham- many). pH, pCO2, and pO2 from venous blood burg, Germany). The level of spinal anesthesia was were evaluated by a blood gas analyzer (Ciba determined by checking sensibility in both direc- Corning 288, Ciba Corning Diagnostics AG, Dietli- tions (upwards and downwards) with a cold test kon, Switzerland). roll (No. 2090, Nizell, Rickenbach, Switzerland) temperated at 4 1C. Return/loss of cold discrimina- tion was defined as the level of the block and Statistical analysis recorded before incision (once the block was estab- Because the variability of the target parameter was lished and the patients hemodynamically stable) as unknown, sample size calculation was not possible. well as immediately post-operative (0 h post-OP). Nonetheless, 25 patients were included in the If blood pressure decreased by more than 20% as study, which seemed likely to be sufficient for compared with baseline values, the patient re- this sort of natural history study. Statistical ana- ceived 5 mg amezinium metilsulfate intravenously lysis was explorative. We calculated the minimum, s (i.v). (Supratonin ,Gru¨ nenthal GmbH, Aachen, maximum, median, arithmetic mean, interquartile 488 Catecholamines in the cerebrospinal fluid range, and standard deviation for each numeric resulting in a median pain score of VAS 3 [2;4] 6 h parameter. Results are presented as median [inter- post-OP, and VAS 2 [1;3] 24 h post-OP. quartile range]. In most patients, dopamine, and epinephrine Because most parameters were not normally