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 variabilityAssessment of autonomic cardiac control  Skin ConductanceAssessment of palmar sweat gland filling as indicator of changed skin sympathetic activity  Blood pressure, heart rate, respiration rateSurrogate 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 well 1. 1 Ledowski 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)

Methods: Catecholamines  T1Recovery 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 HPLC 2 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 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 Even though adrenaline, HR, RR and parameters of HRV are commonly used as surrogate measures of pain, the findings in our study do not support this practice as these parameters dod not reliably reflect different states of pain. Noradrenaline but not adrenaline levels 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 proved the often assumed correlation of especially cardiac sympathetic stress response to different states of acute pain to be either non existing or at least very small. Based on this, traditional physiological measures of pain are unlikely to be useful means of pain assessment in uncommunicative patients. In contrast, it must be acknowledged that the absence of signs of a sympathetic stress response can not be seen as guarantee for the absence of significant acute pain.  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