Division of serratus anterior and the latissimus dorsi muscles during posterolateral thoracotomy is thought to be related with major postoperative acute and chronic pain.

In muscle-sparing thoracotomy, usually two rib retractors are used instead just one: a small Finochietto rib retractor is positioned within the interspace to widen the intercostal opening; then, a second Finochietto retractor is positioned in a right-angled overlapping fashion with respect to the first retractor to displace the serratus anterior and the latissimus dorsi muscles posteriorly and the pectoralis major muscle anteriorly. During muscle-sparing incisions is necessary to spread the ribs wider apart than in a posterolateral thoracotomy in order to compensate for diminished field of view; in addiction, the use of two rib retractors to displace muscles cause injury to the nerves that would affect muscle function. The most obvious example of this would be injury to the long thoracic nerve, with resulting winged scapula.

#### **3.1 Intercostal nerve protecting surgical techniques**

The nerve damage is not significantly associated with most factors except for the technique of closure of the intercostal space: interrupted pericostal sutures are associated with 78% of the low nerve damage and 40% of the high nerve damage.

There are a few prospective studies regarding intercostal nerve protection during thoracotomy closure. Cerfolio et al., 2003, operated on 140 patients who underwent chest closure with pericostal sutures (placed on top of the fifth and seventh ribs) and compared to another 140 patients who underwent chest closure with intracostal sutures (placed on top of the fifth rib and through the small holes drilled in the bed of the sixth rib). They concluded that intracostal sutures were less painful than pericostal sutures, as evaluated at 2 weeks, 1 month, 2 months and 3 month after thoracotomy.

More recently, Bayram et al., 2011, compared two groups of patients who underwent posterior muscle-sparing minithoracotomy in the fifth interspace; in the patients of the group A, two holes were drilled into the sixth rib and sutures were passed through these holes and were circled from the upper edge of the fifth rib, thereby compressing the intercostal nerve underneath the fifth rib. In the group B, the intercostal muscle underneath the fifth rib was partially dissected along with the intercostal nerve, corresponding to the holes on the sixth rib, preventing fifth intercostal nerve compression. Patients of the group B had less post-operative pain as showed lower visual analog scores (VAS) at rest and during coughing.

The conception of a single intercostal nerve running the length of the space is incorrect. Before reaching the angle of the rib, the trunk of the intercostal nerve gives off a branch to the external intercostal muscle and then divides into three main branches:

An upper branch (anterior cutaneous) which occupies the subcostal groove and is the principal or main nerve.

A lower branch which runs for a varying distance along the upper border of the rib below (collateral nerve).

The frequencies of chronic pain and shoulder dysfunction assessed 1 year after operation

Division of serratus anterior and the latissimus dorsi muscles during posterolateral thoracotomy is thought to be related with major postoperative acute and chronic pain.

In muscle-sparing thoracotomy, usually two rib retractors are used instead just one: a small Finochietto rib retractor is positioned within the interspace to widen the intercostal opening; then, a second Finochietto retractor is positioned in a right-angled overlapping fashion with respect to the first retractor to displace the serratus anterior and the latissimus dorsi muscles posteriorly and the pectoralis major muscle anteriorly. During muscle-sparing incisions is necessary to spread the ribs wider apart than in a posterolateral thoracotomy in order to compensate for diminished field of view; in addiction, the use of two rib retractors to displace muscles cause injury to the nerves that would affect muscle function. The most obvious example of this would be injury to the long thoracic nerve, with resulting winged

The nerve damage is not significantly associated with most factors except for the technique of closure of the intercostal space: interrupted pericostal sutures are associated with 78% of

There are a few prospective studies regarding intercostal nerve protection during thoracotomy closure. Cerfolio et al., 2003, operated on 140 patients who underwent chest closure with pericostal sutures (placed on top of the fifth and seventh ribs) and compared to another 140 patients who underwent chest closure with intracostal sutures (placed on top of the fifth rib and through the small holes drilled in the bed of the sixth rib). They concluded that intracostal sutures were less painful than pericostal sutures, as evaluated at 2 weeks, 1

More recently, Bayram et al., 2011, compared two groups of patients who underwent posterior muscle-sparing minithoracotomy in the fifth interspace; in the patients of the group A, two holes were drilled into the sixth rib and sutures were passed through these holes and were circled from the upper edge of the fifth rib, thereby compressing the intercostal nerve underneath the fifth rib. In the group B, the intercostal muscle underneath the fifth rib was partially dissected along with the intercostal nerve, corresponding to the holes on the sixth rib, preventing fifth intercostal nerve compression. Patients of the group B had less post-operative pain as showed lower visual analog scores

The conception of a single intercostal nerve running the length of the space is incorrect. Before reaching the angle of the rib, the trunk of the intercostal nerve gives off a branch to

An upper branch (anterior cutaneous) which occupies the subcostal groove and is the

A lower branch which runs for a varying distance along the upper border of the rib below

the external intercostal muscle and then divides into three main branches:

were also similar between thoracotomy groups.

**3.1 Intercostal nerve protecting surgical techniques**

the low nerve damage and 40% of the high nerve damage.

month, 2 months and 3 month after thoracotomy.

(VAS) at rest and during coughing.

principal or main nerve.

(collateral nerve).

scapula.

An intermediate, the lateral cutaneous branch, which remains in the deep plane with the other branches until it reaches the level of its exits from the space, where it pierces the internal and external intercostal muscles obliquely ( Davies et al, 1932).

In a recent report (McAllister et al, 2011), cadaveric dissections of the 11th intercostal space were performed to characterize intercostal nerve, artery and vein in relationship to the 11th and 12th ribs, in order to access the upper pole of the kidney and realize percutaneous nephrolitostomy. Access placements lateral to the paraspinous muscles and in the lower half of the 11th intercostal space may decrease damage to the intercostal artery and nerve. So far, there are not similar studies in chest wall anatomy to reduce the damage of the intercostal nerves in VATS.

#### **3.2 Video-Assisted Thoracic Surgery**

Video-Assisted Thoracic Surgery (VATS) strongly reduces patient postoperative pain, hospital stay and analgesic requirements when compared to open surgery (Hazelrigg et al., 2000); however, over 50% of patients treated by VATS for spontaneous pneumothorax, complain of post-operative chest wall paresthesia related to the portal sites (Sihoe et al., 2004).

In order to improve the results of VATS, smaller instruments and scopes had been used.

Needlescopic instruments (2 mm) have been applied in treating primary spontaneous pneumothorax resulted in better cosmesis and less postoperative pain (Chen et al., 2003).

However, the incidence and nature of paresthesia remains similar even if the level of surgical trauma is further reduced by performing needlescopic VATS. After a needlescopic VATS sympathectomy (T2-T4) for palmar hyperhidrosis study, Sihoe et al., 2005, founded that 50% of patients complained of some type of paresthesic discomfort in the chest: bloating (41.2%), pins and needles (35.5%) or numbness (23.5%).

Moreover, pre-emptive wound infiltration with local anesthetic (0.5% bupivacaine) reduced post-operative wound pain but not reduced chest wall paresthesia in patients who underwent needlescopic VATS sympathectomy for palmar hyperhidrosis (Sihoe et al., 2007).

It may be hypothesized that perhaps the local anesthesia was effective in blocking the sensitization to pain by sharp wound incision, but was less effective in preventing paresthesia which results from blunt trauma and compression to the intercostal nerves.

Although VATS is a minimal invasive surgery procedure, it not eliminates intercostal nerve injury since the scopes are heavily manipulated during procedure, which may cause the nerve to be crushed against the adjacent rib (figure 1).

Nowdays trend in VATS is to use fewer working ports to reduce even more postoperative pain, chest wall paresthesia and hospital stay.

One study compared one and two ports techniques for VATS thoracic sympathectomies; one-port group showed advantages in terms of hospital stay, rate of post-operative pneumothorax and the need for chest drain insertion (Murphy et al., 2006).

Chest Wall Paraesthesia After Thoracic Surgery 23

Fig. 2. Thoracoscope, stapler and endograsper introduced through the SILS™ port, lined up

Trauma to the intercostal nerves should be minimized by using 5 mm ports for thoracoscope and instruments whenever possible. The long-standing presence of the 10 mm thoracoscope torquing in a small intercostal space could well be responsible for the chronic pain syndrome. Large port sleeves should be avoided with the only exception to the 12 mm port for the linear stapler; however the stapler does not remain in the intercostal space for any

Pre-operative pain is one of the best predictors of severe pain in the early post-operative period; a possible explanation for that is that chronic noxious afferent input has produced neuroplastic changes in the spinal cord (sensitization by upregulation of receptor subsystems) that become manifest as relatively hyperpathic state in the post-operative period. One clinical trial has demonstrated that the severe post-operative pain early after awakening from general anesthesia can be predicted at the pre-operative visit with a scoring rule, using the pain domain of the quality of life questionnaire Short form 36 (SF-36) and the Amsterdam Pre-operative Anxiety and information scale (APAIS),

The transition of acute to chronic post-surgical pain is a complex and poorly understood process, involving biological, psychological and social-environmental factors. Several psychosocial predictors of chronic post-surgical pain have been identified, including increased pre-operative state anxiety, an introverted personality, social support, fear of surgery and "psychic vulnerability", a construct similar to neuroticism (Katz et al., 2009).

**4. Pre-operative prediction of postoperative chronic pain**

along the intercostal space.

prolonged time.

(Kalkman et al., 2003).

Fig. 1. Intercostal nerve compressed (black arrows) between a rigid port and the 5th rib.

In 1998 was described for the first time the technique of single incision thoracic surgery for pneumothorax in six patients (Yamamoto et al., 1998). The authors were able to introduce a bronchoscope, a grasper and a stapler through a 2 cm long incision in the fifth intercostal space in the midaxillary line.

In other report, single incision VATS technique for spontaneous pneumothorax was used in 16 patients and compared retrospectively to 19 patients who underwent the standard three ports VATS technique; single incision VATS group showed less postoperative pain and lower incidence of residual paresthesias (Jutley et al., 2005).

A prospective no randomized trial, compared 28 patients operated on for spontaneous pneumothorax performing single incision thoracic technique (without protecting sleeves) with23 patients operated on with the standard three port VATS technique; the authors reported no increase of surgical costs, shorter hospital stay and decreased rate of chest wall paraesthesias (35%), in the single incision group (Salati et al., 2008).

The authors (Berlanga & Gigirey, 2011), reported an original technique of uniportal VATS for spontaneous pneumothorax using a single flexible laparoscopic in thirteen patients (Figure 2); three patients (23%) presented mild chest wall paresthesia (numbness); two of them were transient paresthesias and the other one was successfully treated whit a eightweek course of Gabapentin (900 mg/day in 3 doses).

The use of this single flexible port (SILS port™) in VATS procedures protects the intercostal nerves from compression due torquing of the camera or instruments and therefore reduces postoperative pain and rate of residual chest wall paresthesias.

Fig. 1. Intercostal nerve compressed (black arrows) between a rigid port and the 5th rib.

space in the midaxillary line.

lower incidence of residual paresthesias (Jutley et al., 2005).

week course of Gabapentin (900 mg/day in 3 doses).

postoperative pain and rate of residual chest wall paresthesias.

paraesthesias (35%), in the single incision group (Salati et al., 2008).

In 1998 was described for the first time the technique of single incision thoracic surgery for pneumothorax in six patients (Yamamoto et al., 1998). The authors were able to introduce a bronchoscope, a grasper and a stapler through a 2 cm long incision in the fifth intercostal

In other report, single incision VATS technique for spontaneous pneumothorax was used in 16 patients and compared retrospectively to 19 patients who underwent the standard three ports VATS technique; single incision VATS group showed less postoperative pain and

A prospective no randomized trial, compared 28 patients operated on for spontaneous pneumothorax performing single incision thoracic technique (without protecting sleeves) with23 patients operated on with the standard three port VATS technique; the authors reported no increase of surgical costs, shorter hospital stay and decreased rate of chest wall

The authors (Berlanga & Gigirey, 2011), reported an original technique of uniportal VATS for spontaneous pneumothorax using a single flexible laparoscopic in thirteen patients (Figure 2); three patients (23%) presented mild chest wall paresthesia (numbness); two of them were transient paresthesias and the other one was successfully treated whit a eight-

The use of this single flexible port (SILS port™) in VATS procedures protects the intercostal nerves from compression due torquing of the camera or instruments and therefore reduces

Fig. 2. Thoracoscope, stapler and endograsper introduced through the SILS™ port, lined up along the intercostal space.

Trauma to the intercostal nerves should be minimized by using 5 mm ports for thoracoscope and instruments whenever possible. The long-standing presence of the 10 mm thoracoscope torquing in a small intercostal space could well be responsible for the chronic pain syndrome.

Large port sleeves should be avoided with the only exception to the 12 mm port for the linear stapler; however the stapler does not remain in the intercostal space for any prolonged time.

#### **4. Pre-operative prediction of postoperative chronic pain**

Pre-operative pain is one of the best predictors of severe pain in the early post-operative period; a possible explanation for that is that chronic noxious afferent input has produced neuroplastic changes in the spinal cord (sensitization by upregulation of receptor subsystems) that become manifest as relatively hyperpathic state in the post-operative period. One clinical trial has demonstrated that the severe post-operative pain early after awakening from general anesthesia can be predicted at the pre-operative visit with a scoring rule, using the pain domain of the quality of life questionnaire Short form 36 (SF-36) and the Amsterdam Pre-operative Anxiety and information scale (APAIS), (Kalkman et al., 2003).

The transition of acute to chronic post-surgical pain is a complex and poorly understood process, involving biological, psychological and social-environmental factors. Several psychosocial predictors of chronic post-surgical pain have been identified, including increased pre-operative state anxiety, an introverted personality, social support, fear of surgery and "psychic vulnerability", a construct similar to neuroticism (Katz et al., 2009).

cytokines.

drugs.

pain syndromes.

**6. Antiinflamatory drugs**

inhibitory (opiate) pathways.

release of mediators of inflammation.

**7. Neuropathic pain treatment**

neuropathic medication (Wildgaarg et al., 2010).

degree of tissue injury.

all patients.

Chest Wall Paraesthesia After Thoracic Surgery 25

First, systemic anti-inflammatory action: after a peripheral nerve injury, the site of damage is typified by the activation of resident immune cells and recruitment and proliferation of nonneuronal elements like neutrophils; a number of soluble mediators can be released (IL-1β) which initiate and maintain sensory abnormalities after injury. Similar to high-dose steroids, which have been proven to contribute to analgesia, local anesthetics including bupivacaine, have been shown to cause anti-inflammatory effects, preventing the release of

Secondly, bupivacaine significantly inhibit N-methyl-D-aspartate (NMDA) receptors channel activation, which play an important role in secondary hyperalgesia and chronic

Finally, subanesthetic doses of local anesthetic drugs, block sodium channel suppressing ectopic electrogenesis and may account for analgesic and antihyperalgesic effects of these

Local tissue damage results in inflammation and propagation of stimuli to the central nervous system. These stimuli are modulated by excitatory (N-methyl-D-aspartate) and

Elective surgery provokes an increase in the circulating cytokine levels, especially with regard to interleukin IL-6; the magnitude of the elevation levels is related directly to the

Nagahiro et al. 2001, showed that post-operative pain measurements in VATS patients were significantly less than in posterolateral thoracotomy patients; also the serum interleukin-6 (IL-6) levels in VATS group patients were significantly decreased when compared with IL-6 serum levels in posterolateral thoracotomy group patients. When correlation between pain and cytokines serum levels was studied, a significant correlation was observed with IL-10 in

Analgesia with anti-inflammatory drugs may contribute to attenuate the postoperative inflammatory response and to prevent postoperative pain in patients undergoing thoracotomy. (NSAIDs) work by inhibiting the cyclooxygenase enzyme responsible for the

Patients undergoing thoracotomy showed reduced postoperative pain, reduced analgesic consumption and decreased serum levels of acute phase reactants (IL-6, CPR), when

Chest wall paresthesia may represent a form of neuropathy following thoracic surgery that

The prevalence of post-thoracotomy pain syndrome (PTPS) after 12-36 months of follow-up is persistently high; over 40% of patients still use conventional analgesics, but only 2 % use

flurbiprofen was added to the systemic analgesic therapy (Esme et al., 2011).

requires specific treatment by nonconventional analgesics or opiates drugs.

#### **5. Pre-emptive analgesia**

Maybe the major justification for using pre-emptive anesthesia in thoracic surgery, is the clinical evidence that the decrease in acute post-thoracotomy pain may result in decreased risk of chronic post-thoracotomy pain syndrome.

The factors that affect the transition from acute to chronic pain, were studied in thirty patients who had undergone lateral thoracotomy. Fifty-two percent of these patients reported long-term pain. Early post-operative pain was the only factor that significantly predicted long-term pain. Pain intensity 24 h after surgery, at rest, and after movement, was significantly greater among patients who developed long-term pain compared with painfree patients (Katz et al., 1996).

Thoracic surgery patients treated with multimodal pre-emptive analgesia with morphine, indomethacin and intercostal nerve blockage with 0.5 % bupivacaine, have shown no differences when comparing to control group in regard to postoperative pain VAS scores, PaCO2 values or postoperative spirometry (Kavanagh et al.,1994).

The pre-emptive effects of administering a 72-h epidural infusion of mepivacaine, beginning before surgery were compared to a postoperative epidural mepivacaine infusion in 70 patients who underwent thoracotomy. Follow-up at 3 and 6 months showed a significant reduction in the incidence of chronic post-thoracotomy pain in the group of patients that received the epidural before surgery (Obata et al.,1999).

Similarly, other authors have found satisfying results with pre-operatively initiated thoracic epidural analgesia in controlling post-thoracotomy pain in the acute and long-term period; they founded decreased incidence and intensity of chronic pain when compared to postoperative epidural or IV analgesia (Sentürk et al., 2002).

Conversely, in another prospective study designed to measure the pre-emptive effect of thoracic epidural analgesia, there was no difference in chronic pain incidence when compared axillary muscle-sparing thoracotomy vs. posterolateral thoracotomy (Ochroch et al., 2005).

Pre-emptive analgesia was intended to prevent the establishment of central sensitization caused by incisional and inflammatory injuries.

The results have not shown a major impact on postoperative pain after thoracic surgery, especially in preventing the development of chronic pain.

A possible explanation for the failure of pre-emptive epidural analgesia in prevent chronic post-thoracotomy pain is that the afferent blockage is not complete, given the variety of incoming stimuli that last for at least several days; in addition, is necessary a complete "humoral blockage" of circulating pro-inflammatory cytokines which lead to central COX-2 induction in the CNS (IL-1β-mediated induction of COX-2), contributing to inflammatory pain hypersensitivity (Gerner et al., 2008).

On the other hand, in neuropathic animal pain models using rib retractors, nearly all myelinated fibers are damaged during the course of allodynia and a extensive Wallerian degeneration was observed 14 days post-surgery; if 0.5 % bupivacaine is given systemically before surgery, mechanical allodynia is prevented (Shin et al., 2008).

This antiallodynic effect of bupivacaine, could be explained by three mechanisms:

Maybe the major justification for using pre-emptive anesthesia in thoracic surgery, is the clinical evidence that the decrease in acute post-thoracotomy pain may result in decreased

The factors that affect the transition from acute to chronic pain, were studied in thirty patients who had undergone lateral thoracotomy. Fifty-two percent of these patients reported long-term pain. Early post-operative pain was the only factor that significantly predicted long-term pain. Pain intensity 24 h after surgery, at rest, and after movement, was significantly greater among patients who developed long-term pain compared with pain-

Thoracic surgery patients treated with multimodal pre-emptive analgesia with morphine, indomethacin and intercostal nerve blockage with 0.5 % bupivacaine, have shown no differences when comparing to control group in regard to postoperative pain VAS scores,

The pre-emptive effects of administering a 72-h epidural infusion of mepivacaine, beginning before surgery were compared to a postoperative epidural mepivacaine infusion in 70 patients who underwent thoracotomy. Follow-up at 3 and 6 months showed a significant reduction in the incidence of chronic post-thoracotomy pain in the group of patients that

Similarly, other authors have found satisfying results with pre-operatively initiated thoracic epidural analgesia in controlling post-thoracotomy pain in the acute and long-term period; they founded decreased incidence and intensity of chronic pain when compared to post-

Conversely, in another prospective study designed to measure the pre-emptive effect of thoracic epidural analgesia, there was no difference in chronic pain incidence when compared axillary muscle-sparing thoracotomy vs. posterolateral thoracotomy (Ochroch et al., 2005).

Pre-emptive analgesia was intended to prevent the establishment of central sensitization

The results have not shown a major impact on postoperative pain after thoracic surgery,

A possible explanation for the failure of pre-emptive epidural analgesia in prevent chronic post-thoracotomy pain is that the afferent blockage is not complete, given the variety of incoming stimuli that last for at least several days; in addition, is necessary a complete "humoral blockage" of circulating pro-inflammatory cytokines which lead to central COX-2 induction in the CNS (IL-1β-mediated induction of COX-2), contributing to inflammatory

On the other hand, in neuropathic animal pain models using rib retractors, nearly all myelinated fibers are damaged during the course of allodynia and a extensive Wallerian degeneration was observed 14 days post-surgery; if 0.5 % bupivacaine is given systemically

**5. Pre-emptive analgesia**

free patients (Katz et al., 1996).

risk of chronic post-thoracotomy pain syndrome.

PaCO2 values or postoperative spirometry (Kavanagh et al.,1994).

received the epidural before surgery (Obata et al.,1999).

operative epidural or IV analgesia (Sentürk et al., 2002).

especially in preventing the development of chronic pain.

before surgery, mechanical allodynia is prevented (Shin et al., 2008).

This antiallodynic effect of bupivacaine, could be explained by three mechanisms:

caused by incisional and inflammatory injuries.

pain hypersensitivity (Gerner et al., 2008).

First, systemic anti-inflammatory action: after a peripheral nerve injury, the site of damage is typified by the activation of resident immune cells and recruitment and proliferation of nonneuronal elements like neutrophils; a number of soluble mediators can be released (IL-1β) which initiate and maintain sensory abnormalities after injury. Similar to high-dose steroids, which have been proven to contribute to analgesia, local anesthetics including bupivacaine, have been shown to cause anti-inflammatory effects, preventing the release of cytokines.

Secondly, bupivacaine significantly inhibit N-methyl-D-aspartate (NMDA) receptors channel activation, which play an important role in secondary hyperalgesia and chronic pain syndromes.

Finally, subanesthetic doses of local anesthetic drugs, block sodium channel suppressing ectopic electrogenesis and may account for analgesic and antihyperalgesic effects of these drugs.

#### **6. Antiinflamatory drugs**

Local tissue damage results in inflammation and propagation of stimuli to the central nervous system. These stimuli are modulated by excitatory (N-methyl-D-aspartate) and inhibitory (opiate) pathways.

Elective surgery provokes an increase in the circulating cytokine levels, especially with regard to interleukin IL-6; the magnitude of the elevation levels is related directly to the degree of tissue injury.

Nagahiro et al. 2001, showed that post-operative pain measurements in VATS patients were significantly less than in posterolateral thoracotomy patients; also the serum interleukin-6 (IL-6) levels in VATS group patients were significantly decreased when compared with IL-6 serum levels in posterolateral thoracotomy group patients. When correlation between pain and cytokines serum levels was studied, a significant correlation was observed with IL-10 in all patients.

Analgesia with anti-inflammatory drugs may contribute to attenuate the postoperative inflammatory response and to prevent postoperative pain in patients undergoing thoracotomy. (NSAIDs) work by inhibiting the cyclooxygenase enzyme responsible for the release of mediators of inflammation.

Patients undergoing thoracotomy showed reduced postoperative pain, reduced analgesic consumption and decreased serum levels of acute phase reactants (IL-6, CPR), when flurbiprofen was added to the systemic analgesic therapy (Esme et al., 2011).

#### **7. Neuropathic pain treatment**

Chest wall paresthesia may represent a form of neuropathy following thoracic surgery that requires specific treatment by nonconventional analgesics or opiates drugs.

The prevalence of post-thoracotomy pain syndrome (PTPS) after 12-36 months of follow-up is persistently high; over 40% of patients still use conventional analgesics, but only 2 % use neuropathic medication (Wildgaarg et al., 2010).

Chest Wall Paraesthesia After Thoracic Surgery 27

intact adjacent peripheral nociceptive nerve fibers, aberrant re-innervation and collateral

However, there are two major limitations to its use. First, modest efficacy of lowconcentration capsaicin formulations that are commercially available so far (1% or less), which require repeated daily self-administration. Second, compliance is poor because of

Initial experiences with Capsaicin treatment at high doses (5 - 10 %) require regional

High dose (8%) concentration of capsaicin patch was recently approved in the EU and USA, a single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance and low risk for systemic effects or drug–drug

Post-operative pain in thoracic surgery is mainly nociceptive; however prolonged central sensitization evidenced as hyperalgesia does occur after surgical trauma and intercostal nerve damage; in addition, nonneuropathic pain can also occur following thoracic surgery. Hamada et al. 2000, studied several patients with post-operative chronic pain (PTPS) in which myofascial pain was thought to be a causative component of post-thoracotomy pain syndrome. A trigger point in a taut muscular band within the scapular region was founded in 67% of these patients and was effectively treated with injections of 0.5% bupivacaine. The authors recommended that all PTPS patients should be examined in detail to determinate

Patients with chronic post-operative intercostal neuralgia that not response to medical treatment are candidates to surgical neurectomy. A recent study showed a successfully treatment in 5 patients with neurectomy proximal to the intercostal neurinoma of one or more intercostal nerves and implantation of the cut nerve into the latissimus dorsi muscle

The site of resection along the course of the intercostal nerves is choosed depending upon the location of the patient´s symptoms and the known anatomy of these nerves; if the patient has a pain in a dermatomal pattern but no motor weakness, it may be possible spare the motor portion of the intercostal nerve by resecting only the perforanting lateral cutaneous branch. If the motor function is nonfunctional or is expendable, then the entire intercostal nerve may be resected proximal to the lesion. If the pain is located only

For patient who fails to improve after resection of intercostal nerves, there is still the

sprouting, all of which are defunctionalized by topical capsaicin.

anesthesia to tolerate side effects (Robbins et al., 1998).

whether there is a trigger point in the scapula region.

**9. Surgical treatment for chronic thoracic pain**

anteriorly, then only the anterior cutaneous branch maybe injured.

possibility of doing a dorsal gangliectomy.

intense initial burning effects.

interactions (Anad et al., 2011).

(Williams et al., 2008).

**8. Myofascial associated pain**

#### **7.1 Gabapentin**

Gabapentin is an anticonvulsant drug that has antinoceptive and antihyperalgesic properties and is effective in treating chronic neuropathic pain by acting on an specific receptor (alpha 2 delta subunit of presynaptic type N voltage-dependent calcium channels), which are overexpressed in the dorsal horn of the spinal cord and spinal ganglia in cases of neurological injury (Laird et al., 2000).

There is a wide variability in gabapentin regimes depends on: pre-operative, peri-operative or post-operative long-term treatment, type of surgery, type of post-operative rescue analgesic and reported outcomes.

Differences in gabapentin doses as well as frequency of administration will undoubtedly introduce disparity in the pain outcomes.

A single pre-operative dose of gabapentin, 1200 mg or less, effectively reduced pain intensity and opioid consumption for the first 24 h after surgery (Ho et al., 2006).

Turan et al., 2006, used a peri-operative regimen of gabapentin taking 1200 mg preoperatively, followed by 1200 mg on the morning of the first and second post-operative day.

Others (Fassoulaki et al., 2002) gave their patients 400 mg of gabapentin the night before breast cancer surgery and then 400 mg three times a day for 10 days.

Gabapentin has shown its effectiveness in the treatment of chronic pain after thoracic surgery decreasing, paresthesia around the wound in 75% of cases; 40% of the patients reported at least one minor side effect during treatment (somnolence or dizziness), but only in 6.7% of the patients, gabapentin had to be discontinued because of intolerance of side effects (Sihoe et al., 2006).

Effectiveness of gabapentin was also studied in the treatment of chronic post-throracotomy pain and compared with NSAIDs. Forty patients with posterolateral or lateral thoracotomy were prospectively studied to compare safety and efficacy of gabapentin to naproxen sodium.

Post-operative pain was evaluated by Virtual Analogue Scale (VAS) and the Leeds Assessment of Neuropathic Symptoms and signs (LANSS). At the latest follow up (60th day), the percentage of patients with VAS<5 was 85% in the gabapentin group and 15% in the naproxen group; similarly, the percentage of patients with LANSS score <12 was 85% in the gabapentin group and 0% in the naproxen group (Solak et al., 2007).

Pregabalin is another drug related to Gabapentin, indicated for neuropathic diabetic or postherpetic pain, but is not been well-studied in thoracic surgery patients.

#### **7.2 Capsaicin**

Topical capsaicin has been used as treatment for certain neuropathic pain states.

Its mechanism of action appears to be based on selective stimulation of the neurons of amyelinic fibers C, causing the release of substance P, which would disturb pain transmission to central system causing a desensitization phenomenon.

Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or

Gabapentin is an anticonvulsant drug that has antinoceptive and antihyperalgesic properties and is effective in treating chronic neuropathic pain by acting on an specific receptor (alpha 2 delta subunit of presynaptic type N voltage-dependent calcium channels), which are overexpressed in the dorsal horn of the spinal cord and spinal ganglia in cases of

There is a wide variability in gabapentin regimes depends on: pre-operative, peri-operative or post-operative long-term treatment, type of surgery, type of post-operative rescue

Differences in gabapentin doses as well as frequency of administration will undoubtedly

A single pre-operative dose of gabapentin, 1200 mg or less, effectively reduced pain

Turan et al., 2006, used a peri-operative regimen of gabapentin taking 1200 mg preoperatively, followed by 1200 mg on the morning of the first and second post-operative day. Others (Fassoulaki et al., 2002) gave their patients 400 mg of gabapentin the night before

Gabapentin has shown its effectiveness in the treatment of chronic pain after thoracic surgery decreasing, paresthesia around the wound in 75% of cases; 40% of the patients reported at least one minor side effect during treatment (somnolence or dizziness), but only in 6.7% of the patients, gabapentin had to be discontinued because of intolerance of side

Effectiveness of gabapentin was also studied in the treatment of chronic post-throracotomy pain and compared with NSAIDs. Forty patients with posterolateral or lateral thoracotomy were prospectively studied to compare safety and efficacy of gabapentin to naproxen sodium. Post-operative pain was evaluated by Virtual Analogue Scale (VAS) and the Leeds Assessment of Neuropathic Symptoms and signs (LANSS). At the latest follow up (60th day), the percentage of patients with VAS<5 was 85% in the gabapentin group and 15% in the naproxen group; similarly, the percentage of patients with LANSS score <12 was 85% in

Pregabalin is another drug related to Gabapentin, indicated for neuropathic diabetic or

Its mechanism of action appears to be based on selective stimulation of the neurons of amyelinic fibers C, causing the release of substance P, which would disturb pain

Peripheral neuropathic hypersensitivity is mediated by diverse mechanisms including altered expression of the capsaicin receptor TRPV1 or other key ion channels in affected or

intensity and opioid consumption for the first 24 h after surgery (Ho et al., 2006).

breast cancer surgery and then 400 mg three times a day for 10 days.

the gabapentin group and 0% in the naproxen group (Solak et al., 2007).

transmission to central system causing a desensitization phenomenon.

postherpetic pain, but is not been well-studied in thoracic surgery patients.

Topical capsaicin has been used as treatment for certain neuropathic pain states.

**7.1 Gabapentin**

neurological injury (Laird et al., 2000).

introduce disparity in the pain outcomes.

analgesic and reported outcomes.

effects (Sihoe et al., 2006).

**7.2 Capsaicin**

intact adjacent peripheral nociceptive nerve fibers, aberrant re-innervation and collateral sprouting, all of which are defunctionalized by topical capsaicin.

However, there are two major limitations to its use. First, modest efficacy of lowconcentration capsaicin formulations that are commercially available so far (1% or less), which require repeated daily self-administration. Second, compliance is poor because of intense initial burning effects.

Initial experiences with Capsaicin treatment at high doses (5 - 10 %) require regional anesthesia to tolerate side effects (Robbins et al., 1998).

High dose (8%) concentration of capsaicin patch was recently approved in the EU and USA, a single 60-min application in patients with neuropathic pain produced effective pain relief for up to 12 weeks. Advantages of the high-concentration capsaicin patch include longer duration of effect, patient compliance and low risk for systemic effects or drug–drug interactions (Anad et al., 2011).

### **8. Myofascial associated pain**

Post-operative pain in thoracic surgery is mainly nociceptive; however prolonged central sensitization evidenced as hyperalgesia does occur after surgical trauma and intercostal nerve damage; in addition, nonneuropathic pain can also occur following thoracic surgery.

Hamada et al. 2000, studied several patients with post-operative chronic pain (PTPS) in which myofascial pain was thought to be a causative component of post-thoracotomy pain syndrome. A trigger point in a taut muscular band within the scapular region was founded in 67% of these patients and was effectively treated with injections of 0.5% bupivacaine. The authors recommended that all PTPS patients should be examined in detail to determinate whether there is a trigger point in the scapula region.

#### **9. Surgical treatment for chronic thoracic pain**

Patients with chronic post-operative intercostal neuralgia that not response to medical treatment are candidates to surgical neurectomy. A recent study showed a successfully treatment in 5 patients with neurectomy proximal to the intercostal neurinoma of one or more intercostal nerves and implantation of the cut nerve into the latissimus dorsi muscle (Williams et al., 2008).

The site of resection along the course of the intercostal nerves is choosed depending upon the location of the patient´s symptoms and the known anatomy of these nerves; if the patient has a pain in a dermatomal pattern but no motor weakness, it may be possible spare the motor portion of the intercostal nerve by resecting only the perforanting lateral cutaneous branch. If the motor function is nonfunctional or is expendable, then the entire intercostal nerve may be resected proximal to the lesion. If the pain is located only anteriorly, then only the anterior cutaneous branch maybe injured.

For patient who fails to improve after resection of intercostal nerves, there is still the possibility of doing a dorsal gangliectomy.

Chest Wall Paraesthesia After Thoracic Surgery 29

Genetic association studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology and may point to the novel molecules that

Recent candidate gene studies have identified and replicated the first associations between

Certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury (Dominguez et al., 2008). Human genome-wide association studies of pain phenotypes might identify novel analgesic targets, help to prioritize research among current targets, and increase the likelihood of

A range of genetic variations that alter the effectiveness of analgesic drugs, have been identified. In particular, polymorphisms of the cytochrome P450 enzymes (CYP), which play a key role in the metabolism of many drugs, can affect the efficacy of opiates and NSAIDs. There are some critical regulators of altered pain states, including genes nor normally expressed in the nervous system, but present in cells of the immune system that also are activates in situations of tissue damage. For example, P2RX7, an ATP receptor absent from neurons but present on macrophages and microglia, which is essential for altered

In another experimental model of incisional pain, was demonstrated that the heat allodynia and spontaneous firing of impulses in C-fibers innervating the skin adjacent to the incision, depend on Vanilloid 1 transient receptor potential (Trpv1) receptors, and the allodynia and firing of C-fibers were much reduced in Trpv1 gene knockout mice (Banik et al., 2009).

The sensation of pain in response to a normal non-painful stimulus (allodynia) or to an exaggerated response to slightly painful stimulus (hyperalgesia), especially when

Although no one thoracic surgical technique has been proved to decrease the incidence of chronic pain, intercostal nerve damage due to rib retraction seems involved in the

Video-assisted thoracic surgery reduces postoperative pain, analgesic requirements, hospital stay and the rate of chest paresthesias when compares to open thoracic surgery; residual chest wall paresthesias rate reduces more with the use of flexible ports and uniportal

Neuropathic postoperative pain should be identified and treated with anticonvulsant drugs (gabapentin, pregabalin); topical treatment with high dose capsaicin patchs is a value

Future clinical researches in genetics and immunology will help to identify susceptible phenotypes, polymorphisms and allelic variants associated to develop neuropathic pain, as well as, to identify novel analgesic targets to improve postoperative analgesia or to reduce

mediate neuropathic pain, facilitating its understanding and management.

several common polymorphisms and pain severity in humans.

success for analgesics candidates emerging from animal studies.

inflammatory or neuropathic pain (Foulkes et al., 2008).

accompanied by numbness, is considered diagnostic for nerve injury.

techniques than with the use of needlescopic instruments.

**12. Conclusion**

complement.

mechanical allodynia.

development of neuralgia.

### **10. Immunology**

Hyperalgesia is commonly found in inflammatory pain conditions where damaged tissue is infiltrated with immune system cells, releasing a variety of soluble mediators that act on peripheral neurons. Allodynia may occur when nerves themselves are damaged (neuropathic pain) which occurs in situations such as diabetic neuropathy, HIV-associated neuropathy, or after surgical trauma.

Many inflammatory mediators (IL-1 and PGE2) act direct on sensory neurons and though cascades of second messengers and kinases, altering the sensitivity of both primary transducing receptors and sodium channels required for action potential transmission.

Pro-inflammatory cytokines can also directly activate and modify gene expression in sensory neurones, and there are several sources of these molecules in close proximity to peripheral nerves. Schwann cells, which have often been thought of having only a passive support role for peripheral nerves, are able to secrete pro-inflammatory cytokines, including via a purinergic P2X7-mediated mechanism (Samad et al., 2001).

Administration of growth factors, such as glial cell line-derived neurotrophic factor (GDNF), could prevent injury-induced transcriptional changes in sensory neurons. Other treatment modalities include the prevention of microglial activation with drugs like minocycline or neuroprotective strategies designed to prevent apoptosis in the dorsal root ganglion or dorsal horn.

Some experimental trials have shown the effects of receptor potential vanilloid 1 (TRPV1) antagonist in regard to improve post-operative analgesia or to reduce the mechanical allodynia.

The analgesic effects of a recently developed transient receptor potential vanilloid 1 (TRPV1) antagonist (AMG0347) were studied in an experimental model of incisional pain (Wu C, et al., 2008). The authors founded that AMG0347 decreased capsaicin-induced heat and mechanical hyperalgesia and blocked central and peripheral TRPV1 receptors. Resiniferatoxin (RTX) is very potent vanilloid receptor against molecularly analogous to capsaicin that causes a slow sustained activation of transient receptor potential vanilloid1 (TRPV-1) receptor.

However, RTX has shown controversial results regarding its use in the treatment of experimental models of chronic pain. Others authors reported that RTX intercostal injections causes a transient hyperalgesic response in injured animals and is ineffective in reducing the mechanical allodynia after thoracotomy (Shin et al., 2010).

#### **11. Genetics**

Pain perception is one of the most complicated measurable traits because there is an aggregate of several phenotypes associated with peripheral and central nervous system dynamics, stress responsiveness and inflammatory state.

The manner in which an individual experiences pain and the magnitude of the response to a given pain stimulus may reflect a genetic "set point" in pain sensitivity, irrespective of the degree of tissue damage or inflammation (Diatchenko et al., 2007).

Hyperalgesia is commonly found in inflammatory pain conditions where damaged tissue is infiltrated with immune system cells, releasing a variety of soluble mediators that act on peripheral neurons. Allodynia may occur when nerves themselves are damaged (neuropathic pain) which occurs in situations such as diabetic neuropathy, HIV-associated

Many inflammatory mediators (IL-1 and PGE2) act direct on sensory neurons and though cascades of second messengers and kinases, altering the sensitivity of both primary transducing receptors and sodium channels required for action potential transmission.

Pro-inflammatory cytokines can also directly activate and modify gene expression in sensory neurones, and there are several sources of these molecules in close proximity to peripheral nerves. Schwann cells, which have often been thought of having only a passive support role for peripheral nerves, are able to secrete pro-inflammatory cytokines, including

Administration of growth factors, such as glial cell line-derived neurotrophic factor (GDNF), could prevent injury-induced transcriptional changes in sensory neurons. Other treatment modalities include the prevention of microglial activation with drugs like minocycline or neuroprotective strategies designed to prevent apoptosis in the dorsal root ganglion or

Some experimental trials have shown the effects of receptor potential vanilloid 1 (TRPV1) antagonist in regard to improve post-operative analgesia or to reduce the mechanical

The analgesic effects of a recently developed transient receptor potential vanilloid 1 (TRPV1) antagonist (AMG0347) were studied in an experimental model of incisional pain (Wu C, et al., 2008). The authors founded that AMG0347 decreased capsaicin-induced heat and mechanical hyperalgesia and blocked central and peripheral TRPV1 receptors. Resiniferatoxin (RTX) is very potent vanilloid receptor against molecularly analogous to capsaicin that causes a slow sustained activation of transient receptor potential vanilloid1

However, RTX has shown controversial results regarding its use in the treatment of experimental models of chronic pain. Others authors reported that RTX intercostal injections causes a transient hyperalgesic response in injured animals and is ineffective in reducing the

Pain perception is one of the most complicated measurable traits because there is an aggregate of several phenotypes associated with peripheral and central nervous system

The manner in which an individual experiences pain and the magnitude of the response to a given pain stimulus may reflect a genetic "set point" in pain sensitivity, irrespective of the

via a purinergic P2X7-mediated mechanism (Samad et al., 2001).

mechanical allodynia after thoracotomy (Shin et al., 2010).

dynamics, stress responsiveness and inflammatory state.

degree of tissue damage or inflammation (Diatchenko et al., 2007).

**10. Immunology**

dorsal horn.

allodynia.

(TRPV-1) receptor.

**11. Genetics**

neuropathy, or after surgical trauma.

Genetic association studies of pain pathways have complemented the traditional neuroscience approaches of electrophysiology and pharmacology and may point to the novel molecules that mediate neuropathic pain, facilitating its understanding and management.

Recent candidate gene studies have identified and replicated the first associations between several common polymorphisms and pain severity in humans.

Certain allelic variants of the MHC could influence susceptibility to develop and maintain neuropathic pain-like behavior following peripheral nerve injury (Dominguez et al., 2008).

Human genome-wide association studies of pain phenotypes might identify novel analgesic targets, help to prioritize research among current targets, and increase the likelihood of success for analgesics candidates emerging from animal studies.

A range of genetic variations that alter the effectiveness of analgesic drugs, have been identified. In particular, polymorphisms of the cytochrome P450 enzymes (CYP), which play a key role in the metabolism of many drugs, can affect the efficacy of opiates and NSAIDs.

There are some critical regulators of altered pain states, including genes nor normally expressed in the nervous system, but present in cells of the immune system that also are activates in situations of tissue damage. For example, P2RX7, an ATP receptor absent from neurons but present on macrophages and microglia, which is essential for altered inflammatory or neuropathic pain (Foulkes et al., 2008).

In another experimental model of incisional pain, was demonstrated that the heat allodynia and spontaneous firing of impulses in C-fibers innervating the skin adjacent to the incision, depend on Vanilloid 1 transient receptor potential (Trpv1) receptors, and the allodynia and firing of C-fibers were much reduced in Trpv1 gene knockout mice (Banik et al., 2009).

#### **12. Conclusion**

The sensation of pain in response to a normal non-painful stimulus (allodynia) or to an exaggerated response to slightly painful stimulus (hyperalgesia), especially when accompanied by numbness, is considered diagnostic for nerve injury.

Although no one thoracic surgical technique has been proved to decrease the incidence of chronic pain, intercostal nerve damage due to rib retraction seems involved in the development of neuralgia.

Video-assisted thoracic surgery reduces postoperative pain, analgesic requirements, hospital stay and the rate of chest paresthesias when compares to open thoracic surgery; residual chest wall paresthesias rate reduces more with the use of flexible ports and uniportal techniques than with the use of needlescopic instruments.

Neuropathic postoperative pain should be identified and treated with anticonvulsant drugs (gabapentin, pregabalin); topical treatment with high dose capsaicin patchs is a value complement.

Future clinical researches in genetics and immunology will help to identify susceptible phenotypes, polymorphisms and allelic variants associated to develop neuropathic pain, as well as, to identify novel analgesic targets to improve postoperative analgesia or to reduce mechanical allodynia.

Chest Wall Paraesthesia After Thoracic Surgery 31

Jutley RS, Khalil MW, & Rocco G. Uniportal vs. standard three-port VATS technique for

Kalkman CJ, Visser K, Moen J, & Bonsel DE. Preoperative prediction of severe pain. *Pain*

Katz J, Jackson M, & Kavanagh BP, et al. Acute pain after thoracic surgery predicts long-

Katz J, & Seltzer Z. Transition from acute to chronic postsurgical pain: risk factors and

Kavanagh BP, Katz J, Sandler AN, Nierenberg H, Roger S, Boylan JF, & Laws AK.

Khan IH, McManus KG, McCraith A, & McGuigan JA. Muscle sparing thoracotomy: a

improvement in wound discomfort. *Eur J Cardiothorac Surg* 2000;18:656-661. Laird MA, & Gidal BE. Use of gabapentin in the treatment of neuropathic pain. *Ann*

Landreneau RJ, Pigula F, Luketich JD, Keenan RJ, Bartley S, Fetterman LS, Bowers CM,

Maguire M, Ravenscroft A, Beggs D, & Duffy J. A questionnaire study investigating the

Maguire MF, Latter JA, Mahajan R, Beggs FD, & Duffy JP. A study exploring the role of

McAllister M, Lim K, Torrey R, Chenoweth J, Barker B, & Baldwin D. Intercostal vessels and

Miyazaki T, Sakai T, Tsuchiya T, Yamasaki N, Tagawa T, Mine M, Shibata Y, & Nagayasu T.

Murphy MO, Ghosh J, Khwaja N, Murray D, Halka AT, Carter A, Turner NJ, & Walker MG.

Nagahiro I, Andou A, Aoe M, Sano Y, Date H, & Shimizu N. Pulmonary function,

Ochroch EA, Gottschalk A, Augoustides JG, Aukburg SJ, Kaiser LR, & Shrager JB. Pain and

Robbins WR, Staats PS, Levine J, & Fields H. Treatment of intractable pain with topical large-dose Capsaicin: Preliminary report. *Anesth Analg* 1998;86:579-83.

VATS and conventional procedure. *Ann Thorac Surg* 2001;72:362-365. Obata H, Saito S, & Fujita N. Epidural block with mepivacaine before surgery reduces long-

throracic surgery. *Eur J Thorac Surg* 2011;39:1033-1039.

ablation techniques. *Eur J Cardiothorac Surg* 2006;30:223-227.

term post-thoracotomy pain. *Can J Anaesth* 1999; 46:1127–1132.

Multimodal analgesia before thoracic surgery does not reduce postoperative pain.

biomechanical analysis confirms preservation of muscle strength but no

Weyant RJ, & Ferson P. Acute and chronic morbidity differences between musclesparing and standard lateral thoracotomies. *J Thorac Cardiovasc Surg* 1996;112:1346-

prevalence of the neuropathic component of chronic pain after thoracic surgery.

intercostals nerve damage in chronic pain after thoracic surgery. *Eur J Cardiothorac*

nerves are at risk for injury during supracostal percutaneous nephrolitostomy. *J*

Assessment and follow-up of intercostals nerve damage after video-assisted

Upper dorsal endoscopic thoracic sympathectomy: a comparison of one-and two

postoperative pain, and serum cytokine level after lobectomy: a comparison of

physical function are similar following, muscle-sparing vs. posterolateral

paraesthesia. *Eur J Cardiothorac Surg* 2005;28:43-46.

term post-thoracotomy pain. *Clin J Pain* 1996;12:50-55.

protective factors. *Expert Rev Neurother* 2009;9:723-744.

2003;105:415-423.

*Br J Anaesth* 1994;73:184-189.

*Pharmacother*. 2000;34:802-7.

*Surg* 2006b;29:873-879.

*Urol* 2011;185:329- 334.

*Eur J Cardiothorac Surg*. 2006a;29:800-805.

thoracotomy. *Chest* 2005;128:2664-2670.

1351.

spontaneous pneumothorax: comparison of post-operative pain and residual

#### **13. References**

Anad P & Bley K. Topical capsaicin for pain manegment: therapeutic potential and

Bayram AS, Ozcan M, Kaya FN, & Gebitekin C. Rib approximation without intercostal nerve

Benedetti F, Amanzio M, Casadio C, Filosso PL, Molinatti M, Oliaro A, Pischedda F, &

Benedetti F, Vighetti S, Ricco C, Amanzio M, Bergamasco L, Casadio C, Cianci R, Giobbe R,

Berlanga L, & Gigirey O. Uniportal video-assisted thoracic surgery for primary spontaneous

Cerfolio RJ, Price TN, Bryant AS, Bass CS, & Bartolucci AA. Intracostal sutures decreases the

Davies F, Gladstone RJ, & Stibbe EP. The anatomy of the intercostal nerves. J Anat

Diatchenko L, Nackley AG, Tchvileva IE, Shabalina SA, & Maixner W. Genetic Architecture

Domínguez CA, Lidman O, Hao JX, Diez M, Tuncel J, Olsson T, Wiesenfeld-Hallin Z, Piehl

Esme H, Kesli R, Apillogullari B, Duran FM, & Yoldas B. Effects of Flurbiprofen on CRP, TNF-α, IL-6 and Postoperative Pain of Thoracotomy. *Int J Med* 2011;8:216-221. Fassoulaki A, Patris k, Sarantopoulos C, & Hogan Q. The analgesic effect of gabapentin and mexiletine after breast surgery for cancer. *Anesth Analg* 2002.;95:985-991.

Gerner P. Post-thoracotomy Pain Management Problems. *Anesthesiol Clin* 2008;26:235-367. Gotoda Y, Kambara N, Sakai T, Kishi Y, Kodama K, & Koyama T. The morbidity, time

Hamada H, Moriwaki K, Shiroyama K, Tanaka H, Kawamoto M, & Yuge O. Myofascial pain

Hazelrigg SR, Magee MJ, & Boley TM. (2000). Video-Assisted Spontaneous pneumothorax. In:

RJ, Mack MJ, Naunheim KS, eds. pp. (73-79). Saunders, Philadelphia, PA. Ho KY, Gan TJ, & Habib AS. Gabapentin and postoperative pain – a Systematic review of

F, & Xu XJ. Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of major histocompatibility complex in development of

course and predictive factors for persistent post-thoracotomy pain. *Eur J Pain*

in patients with postthoracotomy pain syndrome. *Reg Anesth Pain Med* 2000;25:302-

*Minimal access cardiothoracic surgery*. Yim APC, Hazerlrigg SR, Izatt MB, Landreneau

mechanism of action of the new high-concentration capsaicin 8% patch. *Br J Anaesth*

compression reduces post-thoracotomy pain: a prospective randomized study. *Eur*

Maggi G. Postoperative pain and superficial abdominal reflexes after posterolateral

Oliaro A, Bergamasco B, & Maggi G. Neurophysiologic assessment of nerve impairment in posterolateral and muscle-sparing thoracotomy. *J Thorac Cardiovasc*

pneumothorax using a single-incision laparoscopic surgery port: a feasible and safe

**13. References**

2011 Aug 17. (Epub ahead of print).

*J Cardiothorac Surg* 2001;39:570-574.

*Surg*.1998;115:841- 847.

1932;66:323-33.

2001:5:89-96.

305.

thoracotomy. *Ann Thorac Surg.* 1997;64:207-10.

procedure. *Surg Endoscopy* 2011;25:2044-2047.

allodynia. *Pain* 2008;136:313-319.

pain of thoracotomy. *Ann Thorac Surg* 2003;776:407-412.

of human pain perception. *Trends Genet* 2007;23:605-607.

Foulkes T, & Wood, JN. (2008) Pain Genes. *PLoS Genet* 4: e1000086.

randomized controlled trials. *Pain* 2006;126:91-101.

**1. Introduction**

discussed separately.

**2. Peripheral nerve blocks**

buttocks (Aldrete 2003; Pong et al. 2009).

all play a part in the spectrum (Aldrete 2003; Garisto et al. 2010).

**3**

*The Netherlands*

**Paraesthesia in Regional Anaesthesia**

Bouman Esther, Gramke Hans-Fritz and Marcus A. Marco

Paraesthesia is commonly defined as an abnormal altered sensation ranging from numbness, to burning, tingling or continual pain (Garisto et al. 2010). In regional anaesthesia there should also be "neural" quality as introduction of a needle can induce other causes of pain e.g. skin, tissue or bone contact. So the definition is slightly modified to a burning, shooting or electric sensation or pain usually radiating periferically e.g. to arms, legs or

The aetiology of paraesthesia related to regional anaesthesia is not fully understood. Direct trauma to nerves, local haemorrhage, hydrostatic pressure and neurotoxicity from the local anaesthetic or other injected substances like preservatives and anti-microbial additives may

During the performance of regional anaesthesia paraesthesia is a frequently reported phenomenon. In the context of paraesthesia two modalities of regional anaesthesia have to be discussed, i.e. the peripheral nerve or conduction block and neuraxial procedures. Both have their own specific clinical indications, applications and complications. Pathophysiology of peripheral nerve injury and spinal cord injury is very similar. However due to the difference in anatomical considerations and applied techniques it will be

Peripheral nerve blocks are used to anaesthetize a part of the body, to avoid or complement general anaesthesia and to benefit from good pain relief postoperatively. They can be used for a wide range of unilateral procedures localized a limited body area varying from local eye blocks to regional anaesthesia of upper or lower extremities and even a block of the abdominal wall is possible. These nerve blocks can be performed at any level in the course of a peripheral nerve e.g. the radial nerve can be anaesthetized at the level of the brachial plexus, the elbow or at the wrist, separately or in adjunct to general anaesthesia. Currently there is an increased interest in all kind of new techniques e.g. transverse abdominus plain (TAP), ilioinguinal, iliohypogastric, lumbar plexus, psoas and paravertebral blocks and the continuous use of peripheral nerve catheters in the ambulatory setting is advocated (Lee et al. 2011). Nerve blocks for chronic pain treatment are beyond the scope of this chapter.

*Department of Anaesthesiology and Pain Treatment, Maastricht University Medical Centre+, Maastricht,*

## **Paraesthesia in Regional Anaesthesia**

Bouman Esther, Gramke Hans-Fritz and Marcus A. Marco

*Department of Anaesthesiology and Pain Treatment, Maastricht University Medical Centre+, Maastricht, The Netherlands*

#### **1. Introduction**

32 Paresthesia

Rogers ML, & Duffy JP. Surgical aspects of chronic post-thoracotomy pain. *Eur J Cardiothorac*

Rogers ML, Hendersion L, Mahajan RP, & Duffy JP. Preliminary findings in

Salati M, Brunelli A, Xiumè F, Refai M, Sciarra V, Soccetti A, & Sabbatini A. Uniportal video

Samad TA, Moore KA, Sapirstein A, Billet S, Allchrone A, Poole S, Bonventre JV, & Woolf

Sentürk M, Ozcan PE, Talu GK, Kiyan E, Cami E, Ozyalcin S, Dilege S, & Pembeci K. The

Shin JW, Pancaro C, Wang CF, & Gerner P. Low-dose systemic bupivacaine prevents the

Shin JW, Pancaro C, Wang CF, & Gerner P. The effects of Resiniferatoxin in an experimental

Sihoe AD, Au SS, Cheung ML, Chow IK, Chu KM, Law CY, Wan M, & Yim AP. Incidence of

Sihoe AD, Cheung C, Lai HK, Lee TW, Thung KH, & Yim, A. Incidence of chest wall

Sihoe AD, Lee TW, Wan IY, Thung KH, & Yim AP. The use of gabapentin for post-operative

Sihoe AD, Manlulu AV, Lee TW, Wan IY, Thung KH, & Yim AP. Pre-emptive local

Solak O. Merin M & Esme H. Effectiveness of gabapentin in the treatment of chronic post-

Wildgaard K, Ravn J, Nikolajsen L, & Jakobsen E. Consequences of persistent pain after lung

Wu C, Gavva NR, & Brennan TJ. Effect of AMG0347, a transient potential type V1 receptor

Yamamoto H, Okada M, Takada M, Mastuoka H, Sakata K, & Kawamura M. Thoracic Surgery Though a Single Skin Incision. *Arch Surg*. 1998;133:145-147.

inflammatory pain hypersensitivity. *Nature* 2001;410:471-475.

rat thoracotomy model. *Anesth Analg* 2010;110:228-232.

pneumothorax. *Eur J Cardiovasc Surg* 2004;24:1054-1058.

hyperhidrosis. *Eur J Cardiothorac Surg*. 2005;27:313-319.

controlled trial. *Eur J Cardiothorac Surg* 2007;31:103-108.

throracotomy pain*. Eur J Cardiothoracic Surg* 2007;32:9-12.

neurophysiological assessment of intercostal nerve injury during thoracotomy. *Eur*

assisted thoracic surgery for primary spontaneous pneumothorax: clinical and economic analysis in comparison to the traditional approach. *Interact Cardiovasc*

CJ. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to

effects of three different analgesia techniques on long-term postthoracotomy pain.

development of allodynia after thoracotomy in rats. *Anesth Analg* 2008;107:1587-

chest wall paraesthesia after video assisted surgery for primary spontaneous

paresthesia after needlescopic video-assisted thoracic surgery for palmar

and post-traumatic pain in thoracic surgery patients. *Eur J Cardiothorac Surg*

anesthesia for needlescopic video-assisted thoracic surgery: a randomized

cancer surgery: a nationwide questionnaire study*. Acta Anaesthesiol Scand*

antagonist and morphine on pain behavior after plantar incision. *Anesthesiology*

*Surg*. 2000;18:711-6.

*Thorac Surg* 2008;7:63-66.

*Anesth Analg* 2002;94:11-15.

1591.

2006;29:795- 799.

2010;55:60-68.

2008;108:1100-1108.

*J Cardiothorac Surg* 2002;21:298-301.

Paraesthesia is commonly defined as an abnormal altered sensation ranging from numbness, to burning, tingling or continual pain (Garisto et al. 2010). In regional anaesthesia there should also be "neural" quality as introduction of a needle can induce other causes of pain e.g. skin, tissue or bone contact. So the definition is slightly modified to a burning, shooting or electric sensation or pain usually radiating periferically e.g. to arms, legs or buttocks (Aldrete 2003; Pong et al. 2009).

The aetiology of paraesthesia related to regional anaesthesia is not fully understood. Direct trauma to nerves, local haemorrhage, hydrostatic pressure and neurotoxicity from the local anaesthetic or other injected substances like preservatives and anti-microbial additives may all play a part in the spectrum (Aldrete 2003; Garisto et al. 2010).

During the performance of regional anaesthesia paraesthesia is a frequently reported phenomenon. In the context of paraesthesia two modalities of regional anaesthesia have to be discussed, i.e. the peripheral nerve or conduction block and neuraxial procedures. Both have their own specific clinical indications, applications and complications. Pathophysiology of peripheral nerve injury and spinal cord injury is very similar. However due to the difference in anatomical considerations and applied techniques it will be discussed separately.

#### **2. Peripheral nerve blocks**

Peripheral nerve blocks are used to anaesthetize a part of the body, to avoid or complement general anaesthesia and to benefit from good pain relief postoperatively. They can be used for a wide range of unilateral procedures localized a limited body area varying from local eye blocks to regional anaesthesia of upper or lower extremities and even a block of the abdominal wall is possible. These nerve blocks can be performed at any level in the course of a peripheral nerve e.g. the radial nerve can be anaesthetized at the level of the brachial plexus, the elbow or at the wrist, separately or in adjunct to general anaesthesia. Currently there is an increased interest in all kind of new techniques e.g. transverse abdominus plain (TAP), ilioinguinal, iliohypogastric, lumbar plexus, psoas and paravertebral blocks and the continuous use of peripheral nerve catheters in the ambulatory setting is advocated (Lee et al. 2011). Nerve blocks for chronic pain treatment are beyond the scope of this chapter.

Paraesthesia in Regional Anaesthesia 35

In general patients who already suffer from medical conditions that affect nerve conduction like multiple sclerosis, diabetic neuropathy, spinal stenosis and lumbar root disease, neurotoxic chemotherapy and patients with peripheral vascular disease are more susceptible to peripheral nerve block related complications. This could be due to increased sensitivity of already damaged nerves or altered blood supply (Horlocker 2010; Jeng et al. 2010). Furthermore some of the patients e.g. obese, pregnant and patients that use potent anti-coagulants are more prone to procedure related technical problems, haematoma and multiple attempts (Brull et al. 2007; Watts & Sharma 2007), which are associated with

Data from the ASA closed claims projects (Lee et al. 2011) show that upper extremity blocks are more associated with claims regarding nerve injuries. The most performed types of peripheral blocks were interscalene and axillary nerve blocks and intravenous regional anaesthesia. The interscalene and axillary blocks were responsible for the majority of the claims (42% and 26 % respectively) (Lee et al. 2011). The brachial plexus was most frequently involved (32%) followed by the median nerve (21%), ulnar nerve (16%), spinal cord (8%) and the phrenic nerve (8%) (Lee et al. 2011). One third of these injuries was permanent and /or disabling (Lee et al. 2011). Spinal cord injuries were all associated with permanent damage and were more frequently related with interscalene blocks under general anesthesia. In 68 % of the claims for nerve injury it was designated as block related.

Surgery related risk factors are ill-defined. However there is an association with trauma. Symptoms can be fracture related e.g. radial nerve injury in proximal humerus fractures or cranial nerve injury after Le Fort I osteotomy (Kim et al. 2011). Furthermore nerve injury is associated with the use of surgical instruments, diathermy, stretch, nerve compression, ischemia, the use of a tourniquet, patient positioning e.g. lithotomy position and peripheral nerve protection. However in what extent which factor contributes to nerve damage is

Several mechanisms of nerve injury following surgery under peripheral nerve block have been proposed and described but their relative significance is unknown (Hogan 2008;

In cell cultures local anaesthetics in clinically used concentrations cause cytotoxic effects like inhibition of cell growth, necrosis and apoptosis (Hogan 2008). Furthermore local anaesthetics may cause neural membrane lysis due to detergent properties (Kitagawa et al. 2004). The size of these effects is strongly influenced by a prolonged duration of exposure

**2.3.1 Patient related risk factors**

peripheral nerve injury.

(Lee et al. 2011)

Liguori 2004).

**2.4.1 Neurotoxicity**

**2.3.2 Block related risk factors**

**2.3.3 Surgery related risk factors**

uncertain (Liguori 2004; Watts & Sharma 2007)

**2.4 Pathophysiology of peripheral nerve injury**

#### **2.1 Techniques and approaches localizing peripheral nerves**

There are several techniques to localize peripheral nerves: blind techniques, fascial pops, eliciting paraesthesia, trans- and peri-vascular approaches, electrical nerve stimulation, ultrasound/ ultrasonography with or without electrical nerve stimulation, computer tomography (CT) and magnetic resonance imaging (MRI). The first mentioned techniques are frequently used, however in daily clinical practice CT and MRI are nor practically nor workable in the care of the patient (Wedel 2008).

 Currently more sophisticated techniques are available to clinical practice. Electrical nerve stimulation to elict a motor response of a peripheral nerve is commonly used. However, both techniques are depending on anatomical landmarks and so essentially blind with regard to the nerve itself. The required proximity of the needle to the intended nerve is accompanied by the risk of nerve contact, puncture and damage of related structures. With the use of ultrasound techniques are not blind anymore. Nerves, muscles, blood vessels, pleura and even the spread of local anaesthetic peri-neurally can be visualised (Jeng & Rosenblatt 2011; Marhofer et al. 2010). This does not imply that these techniques are without complications. Although none of the patients suffered from postoperative neurological complications an incidence of unintentional intraneural injection of 17% was reported for ultrasound guided interscalene and supraclavicular nerve blocks (Liu et al. 2011).

There are no safety data available to support one of the mentioned techniques (Chin & Handoll 2011) No technique is proven superior regarding safety and efficacy results are inconsistent (Horlocker 2010). However ultrasounds block peripheral nerve localization showed improved efficacy compared to electrical nerve stimulation techniques in several systematic reviews (Abrahams et al. 2009; Neal, J. M. et al. 2008).

#### **2.2 Paraesthesia and peripheral nerve injury**

Fortunately serious neurological complications associated with regional anaesthesia are rare. But this makes it difficult to obtain reliable data about the actual incidence of peripheral nerve block related neurological symptoms. Recent prospective studies reported an incidence of postoperative neurological symptoms between 8-11% direct postoperatively to 0.6% at 6 months (Fredrickson & Kilfoyle 2009; Liu et al. 2009). The majority of the patients reported transient neurological symptoms varying from tingling to paraesthesia resolving between a few days and several months. In France 2.4 serious injuries per 10.000 peripheral nerve blocks were reported (Auroy et al. 2002) It was noted that in case of serious injury or severe neurological complications, they were often related to paraesthesia during needle insertion or pain during injection of the local anesthetics (Auroy et al. 1997). Though permanent neurological injury after a peripheral nerve block is rare neuropathy was reported < 3:100 (Brull et al. 2007). Recently a prospective Australian audit of more than 7000 peripheral nerve and plexus blocks showed and incidence of 0.4 block related nerve injuries per 1000 blocks (Barrington et al. 2009).

#### **2.3 Risk factors for peripheral nerve injury**

Risk factors known to be involved in peripheral nerve injury can be divided into patient related, block related and surgery related risk factors.

There are several techniques to localize peripheral nerves: blind techniques, fascial pops, eliciting paraesthesia, trans- and peri-vascular approaches, electrical nerve stimulation, ultrasound/ ultrasonography with or without electrical nerve stimulation, computer tomography (CT) and magnetic resonance imaging (MRI). The first mentioned techniques are frequently used, however in daily clinical practice CT and MRI are nor practically nor

In earlier times elicting paraesthesia was the only way to localize a nerve to perform a peripheral conduction block. Currently more sophisticated techniques are available to clinical practice. Electrical nerve stimulation to elict a motor response of a peripheral nerve is commonly used. However, both techniques are depending on anatomical landmarks and so essentially blind with regard to the nerve itself. The required proximity of the needle to the intended nerve is accompanied by the risk of nerve contact, puncture and damage of related structures. With the use of ultrasound techniques are not blind anymore. Nerves, muscles, blood vessels, pleura and even the spread of local anaesthetic peri-neurally can be visualised (Jeng & Rosenblatt 2011; Marhofer et al. 2010). This does not imply that these techniques are without complications. Although none of the patients suffered from postoperative neurological complications an incidence of unintentional intraneural injection of 17% was reported for ultrasound guided interscalene and supraclavicular nerve blocks (Liu et al. 2011). There are no safety data available to support one of the mentioned techniques (Chin & Handoll 2011) No technique is proven superior regarding safety and efficacy results are inconsistent (Horlocker 2010). However ultrasounds block peripheral nerve localization showed improved efficacy compared to electrical nerve stimulation techniques in several

Fortunately serious neurological complications associated with regional anaesthesia are rare. But this makes it difficult to obtain reliable data about the actual incidence of peripheral nerve block related neurological symptoms. Recent prospective studies reported an incidence of postoperative neurological symptoms between 8-11% direct postoperatively to 0.6% at 6 months (Fredrickson & Kilfoyle 2009; Liu et al. 2009). The majority of the patients reported transient neurological symptoms varying from tingling to paraesthesia resolving between a few days and several months. In France 2.4 serious injuries per 10.000 peripheral nerve blocks were reported (Auroy et al. 2002) It was noted that in case of serious injury or severe neurological complications, they were often related to paraesthesia during needle insertion or pain during injection of the local anesthetics (Auroy et al. 1997). Though permanent neurological injury after a peripheral nerve block is rare neuropathy was reported < 3:100 (Brull et al. 2007). Recently a prospective Australian audit of more than 7000 peripheral nerve and plexus blocks showed and incidence of 0.4 block related nerve

Risk factors known to be involved in peripheral nerve injury can be divided into patient

**2.1 Techniques and approaches localizing peripheral nerves**

systematic reviews (Abrahams et al. 2009; Neal, J. M. et al. 2008).

**2.2 Paraesthesia and peripheral nerve injury**

injuries per 1000 blocks (Barrington et al. 2009).

**2.3 Risk factors for peripheral nerve injury**

related, block related and surgery related risk factors.

workable in the care of the patient (Wedel 2008).

#### **2.3.1 Patient related risk factors**

In general patients who already suffer from medical conditions that affect nerve conduction like multiple sclerosis, diabetic neuropathy, spinal stenosis and lumbar root disease, neurotoxic chemotherapy and patients with peripheral vascular disease are more susceptible to peripheral nerve block related complications. This could be due to increased sensitivity of already damaged nerves or altered blood supply (Horlocker 2010; Jeng et al. 2010). Furthermore some of the patients e.g. obese, pregnant and patients that use potent anti-coagulants are more prone to procedure related technical problems, haematoma and multiple attempts (Brull et al. 2007; Watts & Sharma 2007), which are associated with peripheral nerve injury.

#### **2.3.2 Block related risk factors**

Data from the ASA closed claims projects (Lee et al. 2011) show that upper extremity blocks are more associated with claims regarding nerve injuries. The most performed types of peripheral blocks were interscalene and axillary nerve blocks and intravenous regional anaesthesia. The interscalene and axillary blocks were responsible for the majority of the claims (42% and 26 % respectively) (Lee et al. 2011). The brachial plexus was most frequently involved (32%) followed by the median nerve (21%), ulnar nerve (16%), spinal cord (8%) and the phrenic nerve (8%) (Lee et al. 2011). One third of these injuries was permanent and /or disabling (Lee et al. 2011). Spinal cord injuries were all associated with permanent damage and were more frequently related with interscalene blocks under general anesthesia. In 68 % of the claims for nerve injury it was designated as block related. (Lee et al. 2011)

#### **2.3.3 Surgery related risk factors**

Surgery related risk factors are ill-defined. However there is an association with trauma. Symptoms can be fracture related e.g. radial nerve injury in proximal humerus fractures or cranial nerve injury after Le Fort I osteotomy (Kim et al. 2011). Furthermore nerve injury is associated with the use of surgical instruments, diathermy, stretch, nerve compression, ischemia, the use of a tourniquet, patient positioning e.g. lithotomy position and peripheral nerve protection. However in what extent which factor contributes to nerve damage is uncertain (Liguori 2004; Watts & Sharma 2007)

#### **2.4 Pathophysiology of peripheral nerve injury**

Several mechanisms of nerve injury following surgery under peripheral nerve block have been proposed and described but their relative significance is unknown (Hogan 2008; Liguori 2004).

#### **2.4.1 Neurotoxicity**

In cell cultures local anaesthetics in clinically used concentrations cause cytotoxic effects like inhibition of cell growth, necrosis and apoptosis (Hogan 2008). Furthermore local anaesthetics may cause neural membrane lysis due to detergent properties (Kitagawa et al. 2004). The size of these effects is strongly influenced by a prolonged duration of exposure

Paraesthesia in Regional Anaesthesia 37

and bupivacaine decrease neuronal blood flow. However contribution of vasoconstriction to

Haematoma and vascular injury are difficult to classify as they may cause local ischemia but

The best treatment of neurological deficit is prevention and starts with a good pre-operative preparation and complete documentation of the block. This includes information about the pre-existent condition of the patient, concomitant diseases, used techniques, local anaesthetics and adjuvants used, complications or difficulties during the procedure, the efficacy and the duration of the block and the surgical procedure. Direct postoperative follow-up should be performed in all patients. If symptoms occur careful physical examinations should be performed and an expert e.g. neurologist should be consulted. Electrophysiological testing should be performed to define a neurogenic basis of nerve

If compression is suspected ultrasonography or an MRI of the plexus has to be done.

Neuraxial blocks are applied to induce anaesthesia or analgesia in a limited part of the body. Especially patients scheduled for major thoracic or abdominal procedures or procedures in

There are 3 techniques to provide neuraxial blockade: Spinal, epidural and a combination of both for longer lasting analgesia i.e. combined spinal-epidural anaesthesia (CSE) as a needle through needle procedure or with the insertion of a catheter at a different level (Warren

Spinal or dural anaesthesia implies perforation of the dura and arachnoid matter, and after aspiration of cerebrospinal fluid, injection of local anaesthetic. Whereas in epidural anaesthesia the dura remains intact. Spinal anaesthesia is restricted to the lumbar region due to the presence of the conus medullaris at the level of L1-L2 in the adult, but a wide variation exists between as high as T12 to as low as L4. Especially in patients with difficult surface landmarks these anatomical variations can lead to more cephalad needle placement than intended (Neal, J.M 2008). However recently experimental higher spinal techniques are

The epidural space can be accessed at any level up to C7 to induce a segmental anaesthetic block depending on the site of injection of local anaesthetics (Warren 2008). The technique relies on anatomical landmarks for penetration of the ligamentum flavum to localize the epidural space. The ligamentum flavum however fuses not always in the midline, especially in the upper thoracic en cervical levels. Moreover the depth of the epidural space itself decreases from 5-8 mm in the lumbar region to 1-2 mm in the upper thoracic and cervical

peripheral nerve injury has not been proved (Hogan 2008).

may provoke local high pressures as well (Liguori 2004).

(Borgeat 2005; Mayfield 2005; Neal, J. M. et al. 2008)

described in literature (van Zundert et al. 2007).

the lower extremities or pelvis can benefit from these techniques.

**3. Neuraxial block**

regions (Neal, J.M 2008).

2008).

**2.5 Diagnosis and management of peripheral nerve injury**

damage, to localize the site of injury and to define the severity of the injury.

and higher concentration of the local anaesthetics, with in vitro the lowest neurotoxicty for procaine, mepivacaine and lidocaïne compared with ropivacaine and bupivacaine (Hogan 2008; Perez-Castro et al. 2009), however most clinical relevant toxicity is attributed to high concentrations of lidocaïne (Zink & Graf 2003).

In a sciatic nerve rat model direct application of 3% 2-chloroprocaine or 1% tetracaine, but not 2% lidocaïne or 0.75 % bupivacaine resulted in subperineural and endoneural oedema, with mast cell degranulation, proliferation of endoneural fibroblasts, Schwann cell necrosis and axonal dystrophy (Myers et al. 1986). Animal data suggest moreover that amino-ester agents like procaine and tetracaine are more neurotoxic than amino-amide agents like lidocaïne and bupivacaine (Zink & Graf 2003).

Other adjuvants injected together with the local anaesthetic e.g. anti-microbial preservatives added to multi-use vials, anti-oxidants or addition of epinephrine or bicarbonate, may also cause nerve damage (Hogan 2008; Zink & Graf 2003).

#### **2.4.2 Mechanical nerve damage**

Nerve injury from nerve contact or penetration is more likely to result due to sharp-bevelled needles than to blunt bevelled needles. However needle-tip penetration is not always the cause of nerve injury. Penetration of fascicles with or without infusion of saline did not result in changes in microscopy or alterations of diffusion barriers, despite high infusion pressures (Hogan 2008). But nerves are not homogenous structures so it is possible to penetrate a nerve without reaching and damaging a neuronal structure.

High injection pressures moreover are associated with persistent neurological deficits after intra neural injections indicating that the surrounding perineurium is very important to protect the fascicles from the cytotoxic effects of the local anaesthetics (Hogan 2008; Jeng & Rosenblatt 2011).

It remains unclear whether a block technique to elict paraesthesia increases the risk of peripheral nerve injury (Horlocker 2001). Nevertheless peripheral nerve damage remains associated with injection of local anaesthetic and paraesthesia or pain on injection of a local anaesthetic (Auroy et al. 2002; Hogan 2008).

Other mechanisms of mechanical nerve damage include surgical trauma, peri- and postoperative positioning and damage from tourniquets. If the latter is a result of ischemia or mechanical deformation is unclear. However by compression of the nerve under the edge of a pneumatic cuff substantial distortion of myelin lamellae and axonal shrinkage is reported as early as 2-4 hours after tourniquet inflation (Hogan 2008; Liguori 2004).

#### **2.4.3 Ischemia**

The earliest response to ischemia of a peripheral neuron is depolarisation and spontaneous activity, perceived by the patient as paraesthesia. Nerve function is restored completely after ischemia of less than 2 hours and ischemic periods to up to 6 hours failed to produce permanent structural nerve changes. However histological examination showed oedema and fiber degeneration (Hogan 2008). Ischemic injury may result from pressure and volume of the local anesthetic or added vasoconstrictors. Moreover local anaesthetics like lidocaïne

and higher concentration of the local anaesthetics, with in vitro the lowest neurotoxicty for procaine, mepivacaine and lidocaïne compared with ropivacaine and bupivacaine (Hogan 2008; Perez-Castro et al. 2009), however most clinical relevant toxicity is attributed to high

In a sciatic nerve rat model direct application of 3% 2-chloroprocaine or 1% tetracaine, but not 2% lidocaïne or 0.75 % bupivacaine resulted in subperineural and endoneural oedema, with mast cell degranulation, proliferation of endoneural fibroblasts, Schwann cell necrosis and axonal dystrophy (Myers et al. 1986). Animal data suggest moreover that amino-ester agents like procaine and tetracaine are more neurotoxic than amino-amide agents like

Other adjuvants injected together with the local anaesthetic e.g. anti-microbial preservatives added to multi-use vials, anti-oxidants or addition of epinephrine or bicarbonate, may also

Nerve injury from nerve contact or penetration is more likely to result due to sharp-bevelled needles than to blunt bevelled needles. However needle-tip penetration is not always the cause of nerve injury. Penetration of fascicles with or without infusion of saline did not result in changes in microscopy or alterations of diffusion barriers, despite high infusion pressures (Hogan 2008). But nerves are not homogenous structures so it is possible to

High injection pressures moreover are associated with persistent neurological deficits after intra neural injections indicating that the surrounding perineurium is very important to protect the fascicles from the cytotoxic effects of the local anaesthetics (Hogan 2008; Jeng &

It remains unclear whether a block technique to elict paraesthesia increases the risk of peripheral nerve injury (Horlocker 2001). Nevertheless peripheral nerve damage remains associated with injection of local anaesthetic and paraesthesia or pain on injection of a local

Other mechanisms of mechanical nerve damage include surgical trauma, peri- and postoperative positioning and damage from tourniquets. If the latter is a result of ischemia or mechanical deformation is unclear. However by compression of the nerve under the edge of a pneumatic cuff substantial distortion of myelin lamellae and axonal shrinkage is reported

The earliest response to ischemia of a peripheral neuron is depolarisation and spontaneous activity, perceived by the patient as paraesthesia. Nerve function is restored completely after ischemia of less than 2 hours and ischemic periods to up to 6 hours failed to produce permanent structural nerve changes. However histological examination showed oedema and fiber degeneration (Hogan 2008). Ischemic injury may result from pressure and volume of the local anesthetic or added vasoconstrictors. Moreover local anaesthetics like lidocaïne

penetrate a nerve without reaching and damaging a neuronal structure.

as early as 2-4 hours after tourniquet inflation (Hogan 2008; Liguori 2004).

concentrations of lidocaïne (Zink & Graf 2003).

lidocaïne and bupivacaine (Zink & Graf 2003).

anaesthetic (Auroy et al. 2002; Hogan 2008).

**2.4.2 Mechanical nerve damage**

Rosenblatt 2011).

**2.4.3 Ischemia**

cause nerve damage (Hogan 2008; Zink & Graf 2003).

and bupivacaine decrease neuronal blood flow. However contribution of vasoconstriction to peripheral nerve injury has not been proved (Hogan 2008).

Haematoma and vascular injury are difficult to classify as they may cause local ischemia but may provoke local high pressures as well (Liguori 2004).

#### **2.5 Diagnosis and management of peripheral nerve injury**

The best treatment of neurological deficit is prevention and starts with a good pre-operative preparation and complete documentation of the block. This includes information about the pre-existent condition of the patient, concomitant diseases, used techniques, local anaesthetics and adjuvants used, complications or difficulties during the procedure, the efficacy and the duration of the block and the surgical procedure. Direct postoperative follow-up should be performed in all patients. If symptoms occur careful physical examinations should be performed and an expert e.g. neurologist should be consulted. Electrophysiological testing should be performed to define a neurogenic basis of nerve damage, to localize the site of injury and to define the severity of the injury.

If compression is suspected ultrasonography or an MRI of the plexus has to be done. (Borgeat 2005; Mayfield 2005; Neal, J. M. et al. 2008)

#### **3. Neuraxial block**

Neuraxial blocks are applied to induce anaesthesia or analgesia in a limited part of the body. Especially patients scheduled for major thoracic or abdominal procedures or procedures in the lower extremities or pelvis can benefit from these techniques.

There are 3 techniques to provide neuraxial blockade: Spinal, epidural and a combination of both for longer lasting analgesia i.e. combined spinal-epidural anaesthesia (CSE) as a needle through needle procedure or with the insertion of a catheter at a different level (Warren 2008).

Spinal or dural anaesthesia implies perforation of the dura and arachnoid matter, and after aspiration of cerebrospinal fluid, injection of local anaesthetic. Whereas in epidural anaesthesia the dura remains intact. Spinal anaesthesia is restricted to the lumbar region due to the presence of the conus medullaris at the level of L1-L2 in the adult, but a wide variation exists between as high as T12 to as low as L4. Especially in patients with difficult surface landmarks these anatomical variations can lead to more cephalad needle placement than intended (Neal, J.M 2008). However recently experimental higher spinal techniques are described in literature (van Zundert et al. 2007).

The epidural space can be accessed at any level up to C7 to induce a segmental anaesthetic block depending on the site of injection of local anaesthetics (Warren 2008). The technique relies on anatomical landmarks for penetration of the ligamentum flavum to localize the epidural space. The ligamentum flavum however fuses not always in the midline, especially in the upper thoracic en cervical levels. Moreover the depth of the epidural space itself decreases from 5-8 mm in the lumbar region to 1-2 mm in the upper thoracic and cervical regions (Neal, J.M 2008).

Paraesthesia in Regional Anaesthesia 39

Other possible causes are direct needle trauma, neural ischemia secondary to sciatic stretching, patient positioning, pooling of local anaesthetics, muscle spasm, early

Treatment can be very difficult. In general non-steroidal anti-inflammatory drugs are prescribed; occasionally opioids are necessary to treat the symptoms. Prevention is essential as treatment is not always successful. If neurological examination is abnormal other possible complications have to be ruled out e.g. epidural haematoma or nerve root damage (Pollock

Although rare, if neurological deficits occur serious complications have to be ruled out. Most cases of spinal haematoma are characterized by an acute or subacute course with acute onset of pain at the level of the haemorrhage with more or less severe paralysis with or

Direct neurological or neurosurgical consultation, MRI and neurophysiolocal testing is required because possible treatment options. Decompressive laminectomy for epidural haematoma, antibiotics and possible surgical drainage for epidural abscess and meningitis, hypertensive therapy for anterior spinal artery syndrome are necessary to

A decompressive laminectomy should be done within 6-8 hours after start of the symptoms to avoid permanent spinal cord injury (Kreppel et al. 2003; Neal, J. M. et al. 2008). For spinal nerve injury, adhesive arachnoiditis and cauda equine syndrome no effective treatment is

Epidural abscess and meningitis are not further discussed as there no obvious relation with

Like peripheral nerve injury spinal cord and spinal root injury after the conduct of a neuraxial block has several proposed mechanisms. Sometimes the mechanism is obvious like in case of epidural haematoma, but often the cause of spinal cord injury remains unclear

Mechanical injury of the spinal cord and spinal nerves during of after conduct of a neuraxial

The vertebral column protects spinal cord and spinal nerves to mechanical injury. To perform a neuraxial block it is necessary to precisely avoid this defence. The access to the spinal canal is based on landmark techniques, but ultrasound becomes more common practice (Balki 2010; Perlas 2010). However as earlier indicated human anatomy varies and this can lead to failure to contact identifiable landmarks, unintentional cephalad needle

**3.5 Pathophysiology of spinal cord, spinal root and spinal nerve injury**

**3.5.1 Mechanical injury of the spinal cord and spinal nerve damage**

mobilization and irritation of the dorsal root ganglion (Pollock 2003).

without bladder/intestinal disturbances (Kreppel et al. 2003).

**3.4 Serious neurological complications**

available (Naguib et al. 1998; Pollock 2003).

block can be caused by several mechanisms.

placement, and unintentional penetration of the dura.

2003).

reduce morbidity.

paraesthesia.

of multifactorial.

#### **3.1 Paraesthesia and the neuraxial block**

In contrast to the peripheral conduction block elicting paraesthesia for neuraxial block is never aimed for. As there are no nerve roots in the posterior epidural space the occurrence of paraesthesia implies perforation of the dural sac with direct contact or puncture of the spinal cord, intrathecal contact with nerve roots, or, more frequently, extradurally contact with an exciting nerve root. Paraesthesia usually does not lead to neurological sequelae but is an unpleasant sensation for the patient and the significance still remains unclear (Aldrete 2003; Neal, J.M 2008).

#### **3.2 Paraesthesia and spinal, epidural and combined spinal epidural anaesthesia**

Reported incidences of paraesthesia vary between 0.2 and 56% depending on approach (Leeda et al. 2005), patient characteristics (Hebl et al. 2010; Spiegel et al. 2009), technique (Hebl et al. 2006; McAndrew & Harms 2003; van den Berg et al. 2011), different catheters (Bouman et al. 2007; Jaime et al. 2000)and depth of insertion (Cartagena & Gaiser 2005). Even an incidence as high as 81% -89% was reported (Hetherington et al. 1994; van den Berg et al. 2005).

The symptoms of paraesthesia during conduct of neuraxial anaesthesia are frequently mild and transient. However sometimes they are so intense that the procedure must be aborted. Fortunately the incidence of permanent neurological damage of 1:20.000-30.000 for spinal anaesthesia and 1:25.000 for obstetric epidurals and 1:3600 in other epidurals remains low (Moen et al. 2004), but in France two thirds of the patients with neurological deficits reported paraesthesia during needle placement or pain on injectionof local anaesthetics (Auroy et al. 1997).

Moreover it seems that paraesthesia is like pre-existing neurological disease, degenerative spinal disease, obesity, female sex and anti-coagulation a risk factor for or an indicator of a complicated procedure and therefore for permanent neurological injury (Aldrete 2003; Brull et al. 2007; Fowler 2007).

#### **3.3 Transient neurological symptoms**

Transient neurological symptoms (TNS) were first reported in 1993. After an uneventful spinal anaesthesia and after full recovery, within a few hours symptoms of light to severe pain in the gluteal region (buttocks) radiating to both lower extremities start with a duration of 6 hours up to 5 days. Furthermore no abnormalities on neurological examination, MRI or electrophysiological testing should be demonstrated (Pollock 2003; Zaric & Pace 2009).

The highest incidences of TNS are found in patients with intrathecal lidocaïne undergoing surgery in lithotomy position (30-36%), arthroscopic knee surgery (18-22%), while in patients undergoing other surgery in supine position the incidences are 4-8% (Pollock 2003).

Although interpreted as possible neurotoxicity of lidocaine TNS is associated with all other local anaesthetics however in a lower incidence (Zaric & Pace 2009). Decreasing lidocaïne concentration from 5 to 0.5 % does not decrease the incidence of TNS. Glucose, hyperbaricity and hyperosmolarity are not contributing factors (Pollock 2003).

In contrast to the peripheral conduction block elicting paraesthesia for neuraxial block is never aimed for. As there are no nerve roots in the posterior epidural space the occurrence of paraesthesia implies perforation of the dural sac with direct contact or puncture of the spinal cord, intrathecal contact with nerve roots, or, more frequently, extradurally contact with an exciting nerve root. Paraesthesia usually does not lead to neurological sequelae but is an unpleasant sensation for the patient and the significance still remains unclear (Aldrete

**3.2 Paraesthesia and spinal, epidural and combined spinal epidural anaesthesia**

Reported incidences of paraesthesia vary between 0.2 and 56% depending on approach (Leeda et al. 2005), patient characteristics (Hebl et al. 2010; Spiegel et al. 2009), technique (Hebl et al. 2006; McAndrew & Harms 2003; van den Berg et al. 2011), different catheters (Bouman et al. 2007; Jaime et al. 2000)and depth of insertion (Cartagena & Gaiser 2005). Even an incidence as high as 81% -89% was reported (Hetherington et al. 1994; van den Berg

The symptoms of paraesthesia during conduct of neuraxial anaesthesia are frequently mild and transient. However sometimes they are so intense that the procedure must be aborted. Fortunately the incidence of permanent neurological damage of 1:20.000-30.000 for spinal anaesthesia and 1:25.000 for obstetric epidurals and 1:3600 in other epidurals remains low (Moen et al. 2004), but in France two thirds of the patients with neurological deficits reported paraesthesia during needle placement or pain on injectionof local anaesthetics

Moreover it seems that paraesthesia is like pre-existing neurological disease, degenerative spinal disease, obesity, female sex and anti-coagulation a risk factor for or an indicator of a complicated procedure and therefore for permanent neurological injury (Aldrete 2003; Brull

Transient neurological symptoms (TNS) were first reported in 1993. After an uneventful spinal anaesthesia and after full recovery, within a few hours symptoms of light to severe pain in the gluteal region (buttocks) radiating to both lower extremities start with a duration of 6 hours up to 5 days. Furthermore no abnormalities on neurological examination, MRI or electrophysiological testing should be demonstrated (Pollock 2003; Zaric & Pace 2009).

The highest incidences of TNS are found in patients with intrathecal lidocaïne undergoing surgery in lithotomy position (30-36%), arthroscopic knee surgery (18-22%), while in patients undergoing other surgery in supine position the incidences are 4-8% (Pollock 2003). Although interpreted as possible neurotoxicity of lidocaine TNS is associated with all other local anaesthetics however in a lower incidence (Zaric & Pace 2009). Decreasing lidocaïne concentration from 5 to 0.5 % does not decrease the incidence of TNS. Glucose, hyperbaricity

and hyperosmolarity are not contributing factors (Pollock 2003).

**3.1 Paraesthesia and the neuraxial block**

2003; Neal, J.M 2008).

et al. 2005).

(Auroy et al. 1997).

et al. 2007; Fowler 2007).

**3.3 Transient neurological symptoms**

Other possible causes are direct needle trauma, neural ischemia secondary to sciatic stretching, patient positioning, pooling of local anaesthetics, muscle spasm, early mobilization and irritation of the dorsal root ganglion (Pollock 2003).

Treatment can be very difficult. In general non-steroidal anti-inflammatory drugs are prescribed; occasionally opioids are necessary to treat the symptoms. Prevention is essential as treatment is not always successful. If neurological examination is abnormal other possible complications have to be ruled out e.g. epidural haematoma or nerve root damage (Pollock 2003).

#### **3.4 Serious neurological complications**

Although rare, if neurological deficits occur serious complications have to be ruled out. Most cases of spinal haematoma are characterized by an acute or subacute course with acute onset of pain at the level of the haemorrhage with more or less severe paralysis with or without bladder/intestinal disturbances (Kreppel et al. 2003).

Direct neurological or neurosurgical consultation, MRI and neurophysiolocal testing is required because possible treatment options. Decompressive laminectomy for epidural haematoma, antibiotics and possible surgical drainage for epidural abscess and meningitis, hypertensive therapy for anterior spinal artery syndrome are necessary to reduce morbidity.

A decompressive laminectomy should be done within 6-8 hours after start of the symptoms to avoid permanent spinal cord injury (Kreppel et al. 2003; Neal, J. M. et al. 2008). For spinal nerve injury, adhesive arachnoiditis and cauda equine syndrome no effective treatment is available (Naguib et al. 1998; Pollock 2003).

Epidural abscess and meningitis are not further discussed as there no obvious relation with paraesthesia.

#### **3.5 Pathophysiology of spinal cord, spinal root and spinal nerve injury**

Like peripheral nerve injury spinal cord and spinal root injury after the conduct of a neuraxial block has several proposed mechanisms. Sometimes the mechanism is obvious like in case of epidural haematoma, but often the cause of spinal cord injury remains unclear of multifactorial.

#### **3.5.1 Mechanical injury of the spinal cord and spinal nerve damage**

Mechanical injury of the spinal cord and spinal nerves during of after conduct of a neuraxial block can be caused by several mechanisms.

The vertebral column protects spinal cord and spinal nerves to mechanical injury. To perform a neuraxial block it is necessary to precisely avoid this defence. The access to the spinal canal is based on landmark techniques, but ultrasound becomes more common practice (Balki 2010; Perlas 2010). However as earlier indicated human anatomy varies and this can lead to failure to contact identifiable landmarks, unintentional cephalad needle placement, and unintentional penetration of the dura.

Paraesthesia in Regional Anaesthesia 41

permanent neurological injury. Other risk factors are patient, procedure or block related. Possible causes of neurological injury are mechanical, vascular or ischemia and neurotoxicity. Although rare, if neurological deficits occur serious complications have to be ruled out, by neurological or neurosurgical consultation, and neurophysiolocal testing. This because possible treatment options have to be enforced as soon as possible to minimize morbidity. MRI is the preferred mode of imaging to demonstrate spinal canal pathology. The best treatment of neurological deficit is prevention and starts with a good pre-operative

The authors would like to thank Mrs. Resy VanderBroeck for her valuable comments and

Abrahams, M.S., M.F. Aziz, R.F. Fu & J.L. Horn (2009). "Ultrasound guidance compared

Aldrete, J.A. (2003). "Neurologic deficits and arachnoiditis following neuroaxial anesthesia."

Auroy, Y., D. Benhamou, L. Bargues, C. Ecoffey, B. Falissard, F.J. Mercier, H. Bouaziz & K.

Regional Anesthesia Hotline Service." *Anesthesiology* 975 (5Nov): 1274-1280 Auroy, Y., P. Narchi, A. Messiah, L. Litt, B. Rouvier & K. Samii (1997). "Serious

Balki, M. (2010). "Locating the epidural space in obstetric patients-ultrasound a useful tool: continuing professional development." *Can J Anaesth* 5712 (12Dec): 1111-1126 Barrington, M.J., S.A. Watts, S.R. Gledhill, R.D. Thomas, S.A. Said, G.L. Snyder, V.S. Tay &

Biglioli, P., M. Roberto, A. Cannata, A. Parolari, A. Fumero, F. Grillo, M. Maggioni, G. Coggi

Borgeat, A. (2005). "Neurologic deficit after peripheral nerve block: what to do?" *Minerva*

Bouman, E.A., H.F. Gramke, N. Wetzel, T.H. Vanderbroeck,R. Bruinsma,M. Theunissen,H.E.

with electrical neurostimulation for peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials." *Br J Anaesth* 1023 (3Mar): 408-

Samii (2002). "Major complications of regional anesthesia in France: The SOS

complications related to regional anesthesia: results of a prospective survey in

K. Jamrozik (2009). "Preliminary results of the Australasian Regional Anaesthesia Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications." *Reg Anesth Pain Med* 346 (6Nov-

& R. Spirito (2004). "Upper and lower spinal cord blood supply: the continuity of the anterior spinal artery and the relevance of the lumbar arteries." *J Thorac*

Kerkkamp & M.A. Marcus (2007). "Evaluation of two different epidural catheters in clinical practice. narrowing down the incidence of paresthesia!" *Acta Anaesthesiol*

preparation and complete documentation of the block.

*Acta Anaesthesiol Scand* 471 (1Jan): 3-12

France." *Anesthesiology* 873 (3: 479-486

*Cardiovasc Surg* 1274 (4Apr): 1188-1192

*Anestesiol* 716 (6Jun): 353-355

*Belg* 582 (2: 101-105

**5. Acknowledgements**

**6. References**

417

preparation of the manuscript.

Dec): 534-541

Penetration of the spinal cord can provoke intense pain, pressure or paraesthesia or no sensation at all. After penetration of the spinal cord, damage can occur from injury of neural structures, haematoma, oedema, central syrinx creation, local anaesthetic or adjuvant toxicity or a combination of these factors (Neal, J.M 2008).

Furthermore reduction of the vertebral canal diameter by degenerative changes, intra- and extradural mass lesions e.g. haematoma, and patient positioning may compromise spinal cord blood flow. This by increasing spinal cord or CSF pressure, decreasing arterial inflow and venous outflow leading to spinal cord ischemia, possibly worsened by injected or infused local anaesthetic (Neal, J.M 2008).

#### **3.5.2 Vascular injury**

The spinal cord and cauda equine receive two thirds of their blood supply from the anterior spinal artery (ASA). The lower thoracic and lumbar sacral spinal cord are supplied by the arteria radicularis magna or artery of Adamkiewicz which provides 25-50% of the total spinal cord blood flow (Biglioli et al. 2004; Neal, J.M 2008). Spinal cord blood flow is like the cerebral blood flow auto regulated with mean arterial pressures between 50/60 – 120 mmHg in animal models and hypoperfusion with hypo perfusion is an often suggested cause of spinal cord damage. However in patients undergoing spine surgery prolonged periods of hypotension induced no detectable spinal cord injury, nor is anterior spinal artery syndrome associated with cardiopulmonary bypass or induced hypotension. Nevertheless the diagnosis anterior spinal artery syndrome has been made in cases with unexplained injury associated with neuraxial blocks. Underlying medical conditions like atherosclerosis are more probable explanations than hypotension or vasoactive agents (Neal, J.M 2008).

Direct vascular trauma from midline and paramedian approaches is anatomically unlikely, but possible during lateral or peri-spinal approaches as psoas compartment or celiac plexus blocks, but no human data supports this view (Neal, J.M 2008).

#### **3.5.3 Neurotoxicity**

As earlier mentioned all local anaesthetics have the potential of neurotoxicity. However in clinically used doses local anaesthetics, opioids, adjuvants and preservatives are relatively safe (Hodgson et al. 1999). However after disruption of the blood-spinal cord barrier certain anatomic conditions may contribute to increased susceptibility to injury. The cauda equina consists of partly unmyelinated nerve fibres with a relative high surface area which is exposed to potentially neurotoxic agents. Secondly, nerve roots in the blood-spinal cord barrier lack connective tissue which provides mechanical and metabolic protection compared with peripheral nerves. Furthermore clearance of toxic substances by CSF is not as efficient as vascular clearance which causes spinal cord and spinal nerve roots to be exposed to drug maldistribution and local high drug doses. These factors are believed to have contributed to cases with cauda equina syndrome after spinal anaesthesia with micro catheters (Neal, J.M 2008).

#### **4. Conclusions**

During the conduct of regional anaesthesia paraesthesia is a frequently reported phenomenon. It is a risk factor for or an identifier of a complicated procedure and in such a way for

Penetration of the spinal cord can provoke intense pain, pressure or paraesthesia or no sensation at all. After penetration of the spinal cord, damage can occur from injury of neural structures, haematoma, oedema, central syrinx creation, local anaesthetic or adjuvant

Furthermore reduction of the vertebral canal diameter by degenerative changes, intra- and extradural mass lesions e.g. haematoma, and patient positioning may compromise spinal cord blood flow. This by increasing spinal cord or CSF pressure, decreasing arterial inflow and venous outflow leading to spinal cord ischemia, possibly worsened by injected or

The spinal cord and cauda equine receive two thirds of their blood supply from the anterior spinal artery (ASA). The lower thoracic and lumbar sacral spinal cord are supplied by the arteria radicularis magna or artery of Adamkiewicz which provides 25-50% of the total spinal cord blood flow (Biglioli et al. 2004; Neal, J.M 2008). Spinal cord blood flow is like the cerebral blood flow auto regulated with mean arterial pressures between 50/60 – 120 mmHg in animal models and hypoperfusion with hypo perfusion is an often suggested cause of spinal cord damage. However in patients undergoing spine surgery prolonged periods of hypotension induced no detectable spinal cord injury, nor is anterior spinal artery syndrome associated with cardiopulmonary bypass or induced hypotension. Nevertheless the diagnosis anterior spinal artery syndrome has been made in cases with unexplained injury associated with neuraxial blocks. Underlying medical conditions like atherosclerosis are

more probable explanations than hypotension or vasoactive agents (Neal, J.M 2008).

equina syndrome after spinal anaesthesia with micro catheters (Neal, J.M 2008).

blocks, but no human data supports this view (Neal, J.M 2008).

Direct vascular trauma from midline and paramedian approaches is anatomically unlikely, but possible during lateral or peri-spinal approaches as psoas compartment or celiac plexus

As earlier mentioned all local anaesthetics have the potential of neurotoxicity. However in clinically used doses local anaesthetics, opioids, adjuvants and preservatives are relatively safe (Hodgson et al. 1999). However after disruption of the blood-spinal cord barrier certain anatomic conditions may contribute to increased susceptibility to injury. The cauda equina consists of partly unmyelinated nerve fibres with a relative high surface area which is exposed to potentially neurotoxic agents. Secondly, nerve roots in the blood-spinal cord barrier lack connective tissue which provides mechanical and metabolic protection compared with peripheral nerves. Furthermore clearance of toxic substances by CSF is not as efficient as vascular clearance which causes spinal cord and spinal nerve roots to be exposed to drug maldistribution and local high drug doses. These factors are believed to have contributed to cases with cauda

During the conduct of regional anaesthesia paraesthesia is a frequently reported phenomenon. It is a risk factor for or an identifier of a complicated procedure and in such a way for

toxicity or a combination of these factors (Neal, J.M 2008).

infused local anaesthetic (Neal, J.M 2008).

**3.5.2 Vascular injury**

**3.5.3 Neurotoxicity**

**4. Conclusions**

permanent neurological injury. Other risk factors are patient, procedure or block related. Possible causes of neurological injury are mechanical, vascular or ischemia and neurotoxicity.

Although rare, if neurological deficits occur serious complications have to be ruled out, by neurological or neurosurgical consultation, and neurophysiolocal testing. This because possible treatment options have to be enforced as soon as possible to minimize morbidity. MRI is the preferred mode of imaging to demonstrate spinal canal pathology. The best treatment of neurological deficit is prevention and starts with a good pre-operative preparation and complete documentation of the block.

#### **5. Acknowledgements**

The authors would like to thank Mrs. Resy VanderBroeck for her valuable comments and preparation of the manuscript.

#### **6. References**

Paraesthesia in Regional Anaesthesia 43

Kitagawa, N., M. Oda & T. Totoki (2004). "Possible mechanism of irreversible nerve injury

Kreppel, D., G. Antoniadis & W. Seeling (2003). "Spinal hematoma: a literature survey with

Lee, L.A., K.L. Posner, C.D. Kent & K.B. Domino (2011). "Complications Associated With

Leeda, M.,R. Stienstra, M.S. Arbous, A. Dahan, B. Th Veering, A.G. Burm & J.W. Van Kleef

Liguori, G.A. (2004). "Complications of regional anesthesia: nerve injury and peripheral

Liu, S.S., J.T. YaDeau, P.M. Shaw, S. Wilfred, T. Shetty & M. Gordon (2011). "Incidence of

Liu, S.S., V.M. Zayas, M.A. Gordon, J.C. Beathe, D.B. Maalouf, L. Paroli, G.A. Liguori, J.

Marhofer, P., H. Willschke & S. Kettner (2010). "Current concepts and future trends in ultrasound-guided regional anesthesia." *Curr Opin Anaesthesiol* 235 (5Oct): 632-636 Mayfield, J.B. (2005). "Diagnosis and management of peripheral nerve block complications."

McAndrew, C.R. & P. Harms (2003). "Paraesthesiae during needle-through-needle combined

Moen, V., N. Dahlgren & L. Irestedt (2004). "Severe neurological complications after central neuraxial blockades in Sweden 1990-1999." *Anesthesiology* 1014 (4Oct): 950-959 Myers, R.R., M.W. Kalichman, L.S. Reisner & H.C. Powell (1986). "Neurotoxicity of local

Naguib, M., M.M. Magboul, A.H. Samarkandi & M. Attia (1998). "Adverse effects and drug

Neal, J.M. (2008). "Anatomy and pathophysiology of spinal cord injury associated with

Neal, J.M., C.M. Bernards, A. Hadzic, J.R. Hebl, Q.H. Hogan, T.T. Horlocker, L.A. Lee, J.P.

Perez-Castro, R.,S. Patel, Z.V. Garavito-Aguilar, A. Rosenberg, E. Recio-Pinto, J. Zhang, T.J.

*Anesthesia and Pain Medicine* 335 (52008/10//): 404-415

spinal epidural versus single-shot spinal for elective caesarean section." *Anaesthesia*

anesthetics: altered perineurial permeability, edema, and nerve fiber injury."

interactions associated with local and regional anaesthesia." *Drug Saf* 184 (4Apr):

regional anesthesia and pain medicine." *Reg Anesth Pain Med* 335 (5Sep-Oct): 423-

Rathmell, E.J. Sorenson, S. Suresh & D.J. Wedel (2008). "ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia and Pain Medicine." *Regional*

Blanck & F. Xu (2009). "Cytotoxicity of local anesthetics in human neuronal cells."

disruption." *Anesthesiology* 1004 (4Apr): 962-967

approach." *Eur J Anaesthesiol* 2211 (11Nov): 839-842

neural blockade." *J Neurosurg Anesthesiol* 161 (1Jan): 84-86

neurological symptoms." *Anesth Analg* 1091 (1Jul): 265-271

*Int Anesthesiol Clin* 433 (3Summer): 119-126

*and intensive care* 315 (5Oct): 514-517

*Anesthesiology* 641 (1Jan): 29-35

*Anesth Analg* 1083 (3Mar): 997-1007

221-250

434

*Anesthesiol Clin* 493 (3Summer): 56-67

663 (3Mar): 168-174

meta-analysis of 613 patients." *Neurosurg Rev* 261 (1Jan): 1-49

caused by local anesthetics: detergent properties of local anesthetics and membrane

Peripheral Nerve Blocks: Lessons From the ASA Closed Claims Project." *Int*

(2005). "Lumbar epidural catheter insertion: the midline vs. the paramedian

unintentional intraneural injection and postoperative neurological complications with ultrasound-guided interscalene and supraclavicular nerve blocks." *Anaesthesia*

Ortiz, V. Buschiazzo, J. Ngeow, T. Shetty & J.T. Ya Deau (2009). "A prospective, randomized, controlled trial comparing ultrasound versus nerve stimulator guidance for interscalene block for ambulatory shoulder surgery for postoperative

Brull, R., C.J. McCartney, V.W. Chan & H. El-Beheiry (2007). "Neurological complications

Cartagena, R. & R.R. Gaiser (2005). "Advancing an epidural catheter 10 cm then retracting it

Chin, K.J. & H.H. Handoll (2011). "Single, double or multiple-injection techniques for

Fowler, S.J. (2007). "Risk of a severe neurological complication after regional anesthesia should be individualized." *Anesth Analg* 1053 (3Sep): 880-881; author reply 881 Fredrickson, M.J. & D.H. Kilfoyle (2009). "Neurological complication analysis of 1000

Garisto, G.A., A.S. Gaffen, H.P. Lawrence, H.C. Tenenbaum & D.A. Haas (2010). Occurrence

Hebl, J.R., T.T. Horlocker, S.L. Kopp & D.R. Schroeder (2010). "Neuraxial blockade in

Hebl, J.R., S.L. Kopp, D.R. Schroeder & T.T. Horlocker (2006). "Neurologic complications

Hetherington, R., R.A. Stevens, J.L. White, L. Spitzer & S. Koppel (1994). "Subjective

Hodgson, P.S., J.M. Neal, J.E. Pollock & S.S. Liu (1999). "The neurotoxicity of drugs given

Hogan, Q.H. (2008). "Pathophysiology of peripheral nerve injury during regional

Horlocker, T.T. (2001). "Neurologic complications of neuraxial and peripheral blockade."

Horlocker, T.T. (2010). "Complications of regional anesthesia." *European Journal of Pain*

Jaime, F., G.L. Mandell, M.C. Vallejo & S. Ramanathan (2000). "Uniport soft-tip, open-ended

Jeng, C.L., T.M. Torrillo & M.A. Rosenblatt (2010). "Complications of peripheral nerve

Kim, J.W., B.R. Chin, H.S. Park, S.H. Lee & T.G. Kwon (2011). "Cranial nerve injury after Le

analgesia: a quality assurance study." *J Clin Anesth* 122 (2Mar): 89-93 Jeng, C.L. & M.A. Rosenblatt (2011). "Intraneural injections and regional anesthesia: the

known and the unknown." *Minerva Anestesiol* 771 (1Jan): 54-58

Fort I osteotomy."  *Anesth Analg* 884 (4Apr): 797-809

anesthesia." *Reg Anesth Pain Med* 335 (5Sep-Oct): 435-441

*Canadian Journal of Anesthesia* 48S1 (S1: R72-76

blocks." *Br J Anaesth* 105 Suppl 1Dec): i97-107

*Supplements* 44 (4: 227-234

(4Apr): 965-974

141**:** 836-844.

1519

1294-1299

(4: 284-288.

(72005/11): 528-530

*Cochrane Database Syst Rev* 7: CD003842

prospective study." *Anaesthesia* 648 (8Aug): 836-844

after regional anesthesia: contemporary estimates of risk." *Anesth Analg* 1044

5 cm is no more effective than advancing it 5 cm." *Journal of clinical anesthesia* 177

axillary brachial plexus block for hand, wrist or forearm surgery in adults."

ultrasound guided peripheral nerve blocks for elective orthopaedic surgery: a

of Paresthesia After Dental Local Anesthetic Administration in the United States.

patients with preexisting spinal stenosis, lumbar disk disease, or prior spine surgery: efficacy and neurologic complications." *Anesth Analg* 1116 (6Dec): 1511-

after neuraxial anesthesia or analgesia in patients with preexisting peripheral sensorimotor neuropathy or diabetic polyneuropathy." *Anesth Analg* 1035 (5Nov):

experiences of anesthesiologists undergoing epidural anesthesia." *Reg Anesth.* 194

**1. Introduction**

**2. Definition**

**4**

*João Pessoa, PB,*

*Brazil*

**Paresthesia in Spinal Anesthesia**

Luiz Eduardo Imbelloni and Marildo A. Gouveia

Spinal anesthesia is induced by injecting small amounts of local anesthetic into the cerebrospinal fluid (CSF), which solution must be capable of blocking nerve paths, and non-toxic, that is, it should not hinder the proper functioning of the bulbar centers, or interfere with the metabolic processes of the more important organs. The injection is usually made in the lumbar spine below the level at which the spinal cord ends (L2). Recently the anatomy of the thoracic spinal canal was investigated with magnetic resonance image (RMI) 19 1 and 50 2 patients, and it has been demonstrated the safety of the segmental spinal anesthesia at T10

If the anesthetist has an adequate knowledge of the relevant anatomy, physiology and pharmacology, safe and satisfactory anesthesia can easily be obtained to the mutual satisfaction of the patient, surgeon and anesthetist. To become expert in the art of spinal anesthesia is no simple matter for the beginner, for many solutions and techniques are available and many problems present themselves which form subjects for discussion and disagreement. The literature is abundant, very illuminating and worthy of very close inspection for begin. Direct trauma to nervous tissue may occur at the level of the spinal cord, nerve root, or peripheral nerve. During attempts to insert a spinal needle into the subarachnoid space, patients occasionally experience paresthesia with a report ranging from 6.3% to 20% 5-8. Two thirds of anesthesia related neurological complications are associated with either paresthesia (direct nerve trauma) or pain during injection (intraneural location) 9. Although the etiology of paresthesia has not been precisely determined, the widely held conventional wisdom is that they result from needle to nerve contact. Some anesthesiologists believe paresthesias occur when the needle contacts a spinal nerve within the epidural space or the subarachnoid space and as such indicates that spinal needle is misdirected. Because of this, several authors advocate withdrawing the spinal needle and

Paresthesia during regional anesthesia is an unpleasant sensation for patients and, more importantly, in some cases it is related to neurological injury. Paresthesia is an abnormal condition in which patients feel a sensation of burning, numbness, tingling, itching or prickling. Paresthesia can also be described as a pins-and-needles or skin-crawling

by using the combined spinal-epidural technique 3 or single puncture 4.

redirecting it away from side where the paresthesia occurred 5-9.

*Faculty of Medicine Nova Esperança FAMENE,*

## **Paresthesia in Spinal Anesthesia**

Luiz Eduardo Imbelloni and Marildo A. Gouveia

*Faculty of Medicine Nova Esperança FAMENE, João Pessoa, PB, Brazil*

#### **1. Introduction**

44 Paresthesia

Perlas, A. (2010). "Evidence for the use of ultrasound in neuraxial blocks." *Reg Anesth Pain*

Pollock, J.E. (2003). "Neurotoxicity of intrathecal local anaesthetics and transient

Pong, R.P., B.S. Gmelch & C.M. Bernards (2009). "Does a paresthesia during spinal needle

Spiegel, J.E., A. Vasudevan, Y. Li & P.E. Hess (2009). "A randomized prospective study

van den Berg, A.A., S. Ghatge, G. Armendariz, D. Cornelius & S. Wang (2011). "Responses to

van den Berg, A.A., M. Sadek, S. Swanson & S. Ghatge (2005). "Epidural injection of

van Zundert, A.A., G. Stultiens, J.J. Jakimowicz, D. Peek, W.G. van der Ham, H.H. Korsten

Watts, S.A. & D.J. Sharma (2007). "Long-term neurological complications associated with

Wedel, D.J., Horlocker T.T (2008). Peripheral nerve blocks in *Anesthesiology*. B. D. D. E

Zaric, D. & N.L. Pace (2009). "Transient neurologic symptoms (TNS) following spinal

Zink, W. & B.M. Graf (2003). "[Toxicology of local anesthetics. Clinical, therapeutic and

pathological mechanisms]." *Anaesthesist* 5212 (12Dec): 1102-1123

spinal anaesthesia: a feasibility study." *Br J Anaesth* 985 (5May): 682-686 Warren, D., Liu SS (2008). Neuraxial anesthesia in *Anesthesiology*. B. D. DE Longnecker,

neurological symptoms." *Best Practice & Research Clinical Anaesthesiology* 173 (3: 471-

insertion indicate intrathecal needle placement?" *Reg Anesth Pain Med* 341 (1Jan-

comparing two flexible epidural catheters for labour analgesia." *Br J Anaesth* 1033

dural puncture during institution of combined spinal-epidural analgesia: a comparison of 27 gauge pencil-point and 27 gauge cutting-edge needles." *Anaesth*

lidocaine reduces the response to dural puncture accompanying spinal needle insertion when performing combined spinal-epidural anesthesia." *Anesth Analg*

& J.A. Wildsmith (2007). "Laparoscopic cholecystectomy under segmental thoracic

Newman MF , Zapol WM,978-1008,The McGraw-Hill Companies, ISBN 978 0 07

surgery and peripheral nerve blockade: outcomes after 1065 consecutive blocks."

Longnecker, Newman MF , Zapol WM,1025-1052,The McGraw-Hill Companies,