Continuous Wound Infusion and Postoperative Pain Current status? Pr Patricia Lavand homme Department of Anesthesiology St Luc Hospital University Catholic of Louvain Medical School Brussels, Belgium
Severe postoperative pain (during the first 24h) - Apfelbaum 2003: 35% - Fletcher 2008: 31% (4% at rest; 27% at movement) Anesthesiology 2010
Pain 2011 Major implication of peripheral sensitization at injury site ( peripheral nociceptive inputs driving central sensitization) Major role of deep tissues in sensitization processes Inflammatory component but also ischemic, and neuropathic component Wound itself is able to initiate and to maintain (re-initiate) peripheral and thereby central sensitization processes
Increase of peripheral PGE 2 is associated with pain onset Gordon et al, Clin Pharmacol Ther 2002 Poor functional recovery is associated with increased concentrations of local wound PGE 2 after hip surgery Buvanendran et al, Anesthesiology 2006
Major role of inflammation i.e. PGE in 2 modulating nociceptive transmission responsiveness of primary nociceptors TTX-r currents Changing spinal processing of nociceptive inputs Zeilhofer & Brune, TIPS 2009
Kidd & Urban, Br J Anaesth 2001
J Am Coll Surg 2006 Improved analgesia opioid use and opioid side effects patient satisfaction hospital stay Low technical failure, no systemic toxicity, no increase of wound infection
Liu et al, J Am Coll Surg 2006
Acta Anaesthesiol Scand 2011 Failure to obtain satisfactory pain relief in case of major intraabdominal procedures? e.g. laparotomy for digestive surgery, oncologic gynecological surgery Contribution of parietal pain and visceral pain in the global pain experience after laparotomy?
Major abdominal surgery and Intrawound Analgesia Multiholed KT and KT location Pain scores Rescue opioids Fredman et al. A&A 2001 NO (Epidural KT) Above fascia NO NO Baig et al. + NO 40% J Am Coll Surg 2006 Above fascia Earlier ambulation Polglase et al. + NO Dis Colon Rectum 2007 Above fascia Beaussier et al. + Anesthesiology 2007 Sub-fascial = pre-peritoneal
Beaussier et al. Anesthesiology 2007
CI infusion: 10 ml/h ropivacaine 0.2% vs saline
RAPM 2009 Role of Visceral afferents? Peritoneum?
Anesth Analg 2004 Wound pain triggers reflex spasm of paraspinal muscles pain at rest (first 12h) and at mobilization
Two multiholed KT using Ropivacaine 0.5% 4mL/h (2x 2mL/h) during 48h Benefits versus saline use: - VAS scores - 47% Morphine use at 48h associated with PONV; sedation - time for GI ileus (22h vs 34h) - hospital stay (2.1 days vs 3.2 days)
Lumbotomy for nephrectomy : two multiholed catheters TAP block intraoperative? Forastiere et al. BJA 2008
Local anesthetic effect: local versus systemic effect? Anesth Analg 2011 LA direct block of the transmission of pain LA indirect local anti-inflammatory effect with nociceptors sensitization LA systemic absorption? Same effect of preperitoneal infusion and systemic administration of LA on mechanical and visceral sensitivity Systemic administration ONLY associated to a significant systemic anti-inflammatory effect
Acta Anaesthesiol Scand 2000 - Positive results: 2/5 studies - «results from wound infiltration remain inconclusive»
Lavand homme et al, Anesthesiology 2007 Intrawound diclofenac 150 mg/day above fascia
J Pain 2008 Intrawound fluid Plasma
IV Diclofenac Intrawound Diclofenac Additional 53% morphine sparing effect
Intrawound NSAID (diclofenac): local versus central effects? Postoperative DICLOFENAC 150 mg/24 hours Systemic Plasma levels 100% 150 mg/24h CNS = 15 mg (10%) Intrawound Plasma levels =max 15% 22.5 mg/24h CNS = 2.25 mg (10%)
Gordon et al, Clin Pharmacol Ther 2002 Measurement of local PGE 2 release in the different situations?
Additional mechanism? - Central site of action highly sensitive to NSAID effect? (IT doses = 1/100 systemic doses) - Or other peripheral mechanisms than only COX inhibition? Gordon et al, Clin Pharmacol Ther 2002
Peripheral mechanisms for local diclofenac analgesia? Peripheral COX-1 but not COX-2 are involved in peripheral sensitization and mechanical hyperalgesia after incision in rats (ESA abstract 2010) Decreased local PGE 2 synthesis nociceptors sensitization Functional downregulation of sensitized nociceptors (activation of ATP-sensitized K+ channels / NO mechanism) (Tonussi & Ferreira, Eur J Pharmacol 1994; Alves et al, Life Sci 2004; ESA abstract 2010) Inhibition of local expression ASIC induced by local acidosis/ph changes (Voilley et al, J Neurosci 2001)
Peripheral sensitization WBC Proinflammatory cytokines:il-1b, IL-6, TNF-a COX induction PGE 2 release Longterm effects: impact on central sensitization? Central sensitization Neuronal And Microglial COX induction Spinal PGE 2 release
BUPIVACAINE wound infiltration for 48h at the site of iliac crest bone graft postoperative pain AND incidence of chronic post-surgical pain of neuropathic origin (0% dysesthesia versus 70%) (Singh et al, Spine 2007) Secondary Mechanical Hyperalgesia (clinical expression of central sensitization): NO impact on the extent but incidence at 48h (25% after intrawound ROPI or DICLO vs 43% in controls) Chronic scar pain (% patients) 50 40 30 20 10 Saline Ropivacaine Diclofenac 0 1 month 6 months Lavand homme et al, Anesthesiol 2007
Conclusion Safe technique but quite expensive Needs to be part of a multimodal analgesic regimen for success! Catheter location Many unanswered questions further well designed studies are mandatory Future developments: multiple targets for peripheral analgesics on nociceptors e.g. local cytokine Il-1β plays a major role in incisional pain (Buvanendran & Kroin, Anesth Analg 2010)