**6. Prevention and treatment strategies of PTPS**

#### **6.1 Intra and postoperative analgesia**

Postoperative analgesia is commonly based on the use of regional anesthesia and systemic drug infusion. Different regional anesthesia techniques have been used: mostly thoracic epidural anesthesia (TEA) (58, 59), thoracic paravertebral block (PVB) (60), and, secondarily, pleural infusion or intercostal nerves block. The role of intrapleural infusion, intercostal nerve block and local infiltration in reducing PTPS is still unclear because studies evaluating this analgesic technique are confounding and lacking of exhaustive data (45).

TEA and PVB with opioids and local anesthetics mixture are the most used regional techniques. Nowadays, TEA is still considered the gold standard technique even if PVB has recently emerged as valid alternative to TEA (61).

However the role of TEA in reducing PTPS remains controversial and questionable. In any case, multimodal analgesia using different modalities as regional and systemic analgesic techniques is highly recommended (61).

On the contrary, there is no consensus on the drug to use for adjunct intravenous analgesia. Ketamine has been confirmed as a useful agent (62, 63) while COX-2 inhibitors, celecoxib i.e, were recently proposed as a valid alternative (64). Besides, only few studies reported about the efficacy of the S(+) - isomer of Ketamine (65) that has been demonstrated to have twice the anaesthetic and analgesic potency of the racemic ketamine preparation and is judged to induce less psychic emergence reactions, a reduced number of hallucinations (66) and to be followed by a more rapid recovery of vigilance (67, 68) preserving the hypoxic pulmonary vasoconstriction, enhancing oxygenation and decreasing shunt fractions in monopulmonary ventilation (52).

Only few trials have demonstrated the effect of iv ketamine as an adjunct to TEA. Suzuki et al (69) demonstrated the efficacy of 0,05 mg Kg-1 h-1 racemic ketamine combined with TEA with ropivacaine and morphine on acute pain control until 3 months postoperatively but not at 6 months follow-up. Dualé et al (63) confirmed that racemic ketamine (1mg kg-1h-1 during surgery and 1 mg kg-1h-1 in the first 24 hours) was effective in the immediate postoperative

Post Thoracotomy Pain Syndrome 397

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pain but failed to prevent a reduction of chronic PTPS at 6 weeks and 4 months after surgery.

S-(+)-isomer of Ketamine has been demonstrated to be more effective than the racemic mixture with a lower incidence of side effects. Argiriadou et al (65) recently proposed the use of the S(+)-isomer of Ketamine in conjunction with thoracic paravertebral ropivacaine providing better early postoperative pain relief than ropivacaine alone or in adjunction with perecoxib.

In the last years a great interest has been elicited by the use of the preemptive analgesia and the administration of Ketamine during and after surgery to prevent and lessen the processes involved in the development of neuropathic pain (70) even if some contrasting results have been published on the use of Ketamine for postoperative pain control (71).

Patients treated with TEA in pre-empty modality with opioids and local anesthetics showed a lower incidence of chronic PTPS if compared to patients who received only intravenous opioids (72). Moreover, the exclusive intravenous administration of opioids may induce hyperalgesia and tolerance to opioids themselves, both processes NMDA receptors activation mediated (73).

NMDA receptors antagonists may prevent the acute tolerance to opioids and, among them, ketamine at a blood concentration of 30-120 ng ml-1 is able to strengthen the nociceptives effects of opioids without altering sedation indexes (74).

The preoperative administration of 0.1 mg/Kg epidural ketamine reduced the area affected by hyperalgesia and allodynia around the surgical wound in the first 30 days after incision; the same dosage given intramuscolarly did not produce the same effects (75). The limitations to these observations are that the neuropathic lesion and pain could appear after a period longer than expected (76).

The administration of NMDA receptors inhibition is hampered by the need of a prolonged administration which could be more efficient via an oral route administration (77).

### **7. Conclusions**

Many progresses have been done in the identification and the pathophysiological understanding of PTPS even if we are far from a well defined understanding of this syndrome. From the clinical point of view the priority resides on the continuous collaboration among anesthetists, surgeons, pharmacists and nurses to guarantee to any patient the best approach and the most correct pharmacological therapy.

Multimodal analgesia using different modalities as regional and systemic analgesic techniques is highly recommended (61).

In our opinion, pain unit in the management of patients undergoing thoracotomy is likely to warrant intensive and aggressive pain control with multimodal strategy in order to assure high level of comfort in the perioperative period and consequently reduce the incidence of PTPS.

#### **8. References**


pain but failed to prevent a reduction of chronic PTPS at 6 weeks and 4 months after

S-(+)-isomer of Ketamine has been demonstrated to be more effective than the racemic mixture with a lower incidence of side effects. Argiriadou et al (65) recently proposed the use of the S(+)-isomer of Ketamine in conjunction with thoracic paravertebral ropivacaine providing better early postoperative pain relief than ropivacaine alone or in adjunction with

In the last years a great interest has been elicited by the use of the preemptive analgesia and the administration of Ketamine during and after surgery to prevent and lessen the processes involved in the development of neuropathic pain (70) even if some contrasting results have

Patients treated with TEA in pre-empty modality with opioids and local anesthetics showed a lower incidence of chronic PTPS if compared to patients who received only intravenous opioids (72). Moreover, the exclusive intravenous administration of opioids may induce hyperalgesia and tolerance to opioids themselves, both processes NMDA receptors

NMDA receptors antagonists may prevent the acute tolerance to opioids and, among them, ketamine at a blood concentration of 30-120 ng ml-1 is able to strengthen the nociceptives

The preoperative administration of 0.1 mg/Kg epidural ketamine reduced the area affected by hyperalgesia and allodynia around the surgical wound in the first 30 days after incision; the same dosage given intramuscolarly did not produce the same effects (75). The limitations to these observations are that the neuropathic lesion and pain could appear after

The administration of NMDA receptors inhibition is hampered by the need of a prolonged

Many progresses have been done in the identification and the pathophysiological understanding of PTPS even if we are far from a well defined understanding of this syndrome. From the clinical point of view the priority resides on the continuous collaboration among anesthetists, surgeons, pharmacists and nurses to guarantee to any

Multimodal analgesia using different modalities as regional and systemic analgesic

In our opinion, pain unit in the management of patients undergoing thoracotomy is likely to warrant intensive and aggressive pain control with multimodal strategy in order to assure high level of comfort in the perioperative period and consequently reduce the incidence of

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**7. Conclusions** 

PTPS.

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