effects of acute postoperative pain on catecholamine plasma levels, haemodynamic parameters and...
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Effects of Acute Postoperative Pain on Catecholamine Plasma Levels, Haemodynamic
Parameters and Cardiac Autonomic Control
Thomas Ledowski
Maren Reimer
Venus Chavez
Vimal Kapoor
Manuel Wenk
Background and Objectives
“Objective” Monitors for Nociception/Pain ?
Surgical Pleth Index [SPI] 0-100 score based on pletysmographic assessment of the pulse wave amplitude and heart beat interval
Heart rate variability Assessment of autonomic cardiac control
Skin Conductance Assessment of palmar sweat gland filling as indicator of changed skin sympathetic activity
Blood pressure,heart rate, respiration rate Surrogate parameters for stress/pain (?)
Background and Objectives
All methods are based on one common assumption:
Acute pain provokes the release of stress hormones and influences cardiac and peripheral parameters of sympathetic activity
….and they have also in common that they do not work that well1.
1Ledowski et al. Anaesthesia 2010
Hypothesis
Aim of this trial was to go “back to the roots” and test the hypothesis
“Acute postoperative pain triggers a significant sympathetic stress response”
Hypothesis
Methods: Protocol
Inclusion: 85 patients scheduled for non-emergency, minor (= distal of elbow and knee) plastic and orthopaedic surgery
Exclusion: All medication or clinical conditions known or suspected to interact with catecholamine plasma levels, autonomic cardiac control, heart rate, blood pressure or respiration rate
Protocol: On arrival in recovery and once able to communicate verbally assessment of pain on 0-10 numeric rating scale (NRS). Further pain rating every 5 minutes.
Methods: Haemodynamics and HRV
Parallel to the NRS assessments monitoring of mean arterial pressure (MAP), heart rate (HR), respiration rate (RR) and parameters of Heart Rate Variability (HRV)
Parameter of HRV Definition Clinical Significance
Total Power (TP) 0.04-0.4 Hz Descriptor of overall variability of HRV
Low frequency (LF) 0.04-0.15 Hz Descriptor of sympathetic as well as parasympathetic autonomic influences
High frequency (HF) 0.15-0.4 Hz Descriptor of predominantly vagal cardiac autonomic regulation
Low to high frequency ratio (LF/HF)
Ratio of LF:HF Increased ratio may reflect increased sympathetic predominance in cardiac autonomic control
Ultra short entropy (UsEn) Normalized 0-100% score describing randomness of HRV
UsEn found to decrease with pathology - yet to be further investigated
Methods: Catecholamines
T1 Recovery admission, time of first pain rating
T2-4 (optional) Whenever pain category changed:
no = NRS 0
mild = NRS 1-3
moderate = NRS 4-5
severe = NRS > 5
T5 At time of discharge from recovery room
Samples stored on ice, spun at 4˚C and frozen at -80 ˚C; analysed via solvent extraction method and HPLC2
Normal values 200–600 pg/ml for NA , 10–50 pg/ml for ADR 2 Smedes et al. J Chromatography 1982
Noradrenaline (NA) and Adrenaline (ADR) plasma levels
Results: Decriptives
239 pain readings (15% no, 45% mild, 27% moderate, 13% severe pain)
from 84 patients (71 male/13 female, 31 ± 11 yrs)
Mean theatre time 75 ± 32 min, mean time in recovery 51 ± 25 min
42 orthopaedic and 42 plastic surgery procedures
(1 case excluded)
No correlation between any of the investigated parameters and the severity of pain
Results: Differences at Pain Levels
NRS 0 1-3 4-5 6-10
Noradrenaline[pg ml-1]
743 (101)[545-941]*
909 (69)[773-1046]*
948 (74)[801-1094]
1084 (84)[919-1249]*
Adrenaline [pg ml-1]
193 (102)[0-394]
179 (67)[46-312]
235 (73)[90-380]
188 (85)[21-355]
LF [ms2Hz-1] 799 (343)[121-1477]
1393 (199)[1000-1787]
1256 (238)[786-1726]
909 (314)[290-1529]
HF [ms2Hz-1] 390 (145)[99-681]
507 (91)[327-687]
499 (103)[296-702]
450 (125)[203-696]
LF/HF 5.8 (1.1)[3.6-8.1]
5.6 (0.7)[4.3-6.9]
5.6 (0.8)[4.0-7.1]
6.3 (1.0)[4.2-8.3]
UsEn 48 (2)[44-52]
51 (1.3)[49-54]
51 (1.5)[48-53]
49 (1.7)[45-52]
MAP [mmHg] 97 (2.0)[93-101]*
98 (1.4)[96-101]*
99 (1.5)96-102]
102 (1.6)[99-105]*
HR [min-1] 74 (2.8)[69-80]
68 (1.7)[65-72]
70 (1.9)[66-74]
73 (2.3)[69-77]
RR [min-1] 11 (0.8)[10-13]
11 (0.5)[10-12]
11 (0.6)[10-12]
12 (0.8)[11-14]
Data as mean (SEM)
[95% CI] * P < 0.05
Results: Prediction of Severe Pain
Even though NA and MAP showed some differences between states of pain, their predictive value to identify states of severe pain is not much better than tossing a coin!
Limitations
Limited number of venous blood samples (catecholamines in arterial/mixed venous blood may have detected subtle changes)
Very specific setting: acute postoperative pain - Influence of surgical tissue trauma, anaesthetic agents, arousal, anxiety or agitation on stress response cannot be excluded
Conclusion: Does acute pain not matter?
Conclusion
Noradrenaline plasma levels and MAP were found to be significantly different between the extremes of the NRS, however the magnitude of these differences is of questionable clinical relevance.
Overall, our results suggest that the often assumed
significant contribution of acute pain to the postoperative stress response may be less relevant – in this context, surgical aspects may be much more important
The absence of signs of a sympathetic activation is neither an indicator nor at all a guarantee for the absence of significant
acute pain!
The absence of signs of a sympathetic activation is neither an indicator nor at all a guarantee for the absence of significant acute pain!
Results: Admission vs. Discharge*P < 0.05
vs. severe
Admission
Discharge