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