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
“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
Background and Objectives
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
 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: Protocol
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: Haemodynamics and HRV
Noradrenaline (NA) and Adrenaline (ADR) plasma levels
 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
Methods: Catecholamines
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: Decriptives
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: Differences at Pain Levels
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!
Results: Prediction of Severe Pain
 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
Limitations
Conclusion: Does acute pain not matter?

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!
Conclusion
Admission
Discharge
*P < 0.05
vs. severe
Results: Admission vs. Discharge