Colorectal surgery is a common major abdominal procedure that can be associated with severe pain and a prolonged hospital stay (1). The provision of optimal analgesia is an important facet of patient recovery following colorectal surgery. Epidural analgesia has been shown to provide significantly better pain control during mobilization when compared with systemic patient-controlled morphine analgesia (PCA) for the first two postoperative days after open colonic resection (2-3). Indeed, during the past decade various pathways have been developed for fast-track perioperative care after colonic surgery that employs thoracic epidural analgesia as one of the key elements (4-5). However, several medical conditions preclude the use of epidural analgesia and approximately 20-30% of eligible patients do not benefit from it because of technical problems associated with catheter placement (e.g. leaks, catheters falling out, patchy or unilateral blocks, and catheter occlusions) (6-7). Since placement of the epidural catheter is not without risk for the patient, a number of patients reject this anaesthetic technique. Additionally, there are practical issues such as theatre delays due to time required for insertion of epidurals and postoperative time spent managing problems such as hypotension and incomplete analgesia. Delays in implementing rescue analgesia can be associated with severe pain and suffering. These limitations have stimulated the search for alternative ways of managing pain in the setting of abdominal laparotomy.
Continuous local anaesthetic wound infusions have been shown to be an effective modality for pain management with a very low (approximately 1%) technical failure rate and zero reported toxicity (8-9). Five trials have investigated the analgesic effect of wound infiltration with local anaesthetic after open colonic surgery. In all trials a continuous infusion technique with multiorifice catheters placed subcutaneously (10), above the fascia (11-12), below the fascia (13) or in the pre-peritoneal space were used (14). Only catheters placed below the fascia or in the preperitoneal space had a positive effect on clinical outcome (13-14). Wang et al assessed the of efficacy continuous local anesthetic wound infusion in patients undergoing open colorectal surgery following a midline laparotomy (13). The catheters were inserted by the surgeon following closure of the rectus abdominus muscle by tunnelling the catheters subcutaneously along the length of the wound. The final position of the catheter was at the level of the musculo-fascial closure and not superficial to it. Each catheter was then connected to a continuous infusion of local anesthetic (ropivacaine 0.2% 4ml per hour) or normal saline. Patients in the study group (ropivacaine infusion) used significantly less morphine at 48 h, mobilised earlier and had reduced postoperative ileus. There was no significant effect on time to first bowel motion or length of hospital stay.
Beaussier et al evaluated the role of continuous wound infusion of ropivacaine in patients after open colorectal surgery (14). The study group received a bolus of ropivacaine followed by a continuous infusion of 0.2% ropivacaine 10ml/hr for 48 hours through a multiholed wound catheter placed in the pre-peritoneal space (see Figure 1). The authors assessed in detail relevant outcomes such as opioid (patient controlled analgesia, PCA) sparing, pain at rest and mobilization, sleep quality and recovery of gastrointestinal function. All these measures were significantly improved and there was also a significant reduction in hospital stay (115 vs. 147 h).
The promising results from these trials suggest that for continuous local anaesthetic infusions to be effective the catheter must be placed deep to the fascial layers. Indeed, the analgesic efficacy of catheters placed deep to the fascia/pre-peritoneal space has recently been shown in patients undergoing open nephrectomy and renal transplant surgery (15-16). An additional benefit of continuous pre-peritoneal infusion of ropivacaine is reduced postoperative diaphragmatic dysfunction associated with major open colorectal surgery (17). The encouraging results from these studies and others have prompted some respected authorities to suggest that the pendulum may be swinging towards increased use of continuous local anaesthetic wound infusions (9, 18) and perhaps as an alternative to thoracic epidural infusions (19).
Figure 1: a). Schematic representation of the multiholed catheter placed in the preperitoneal space. The parietal peritoneal membrane is closed with running sutures and a 20-gauge multiholed Soaker catheter is tunneled 3cm from the lower end of the midline incision through an introducer needle. The catheter is positioned between the previously closed parietal peritoneum and the underside of the transversalis fascia along the full length of the wound. b) Photograph of closed peritoneum and introducer in position for catheter placement.
Despite the promising results shown in the study by Beaussier et al there are some intrinsic limitations to its clinical application (14). Primarily these relate to the need for the peritoneal membrane to be closed by the surgeon prior to catheter placement. Closure of the parietal peritoneum adds to surgical time. In patients who have had previous abdominal surgery the parietal peritoneum may not be easily sutured. This may allow leakage of local anaesthetic into the peritoneal cavity. Stretching, suturing and re-approximation of the peritoneum can produce ischaemia and postoperative pain (20). Indeed, the obstetric literature suggests that non-closure of the parietal peritoneum is associated with less postoperative pain and fewer adhesions (21-23). An alternative method of pre-peritoneal catheter placement is the peripheral tunneled technique. The technique is simple to perform and as it does not require resuturing of the peritoneum adds little to the surgical time. Additionally, it can be used in patients who have had previous abdominal surgery and those who require a defunctioning stoma.
Prior to wound closure, the fascia on the opposite side of the surgeon is grasped by an assistant with 2 clamps and elevated. A 20cm tunneling device (obturator and peel-away sheath) is placed through a stab incision at the xiphisternum and guided through the muscle layers and tracked into the pre-peritoneal space. The tunneling device can then be directed along the plane of the pre-peritoneal space towards the iliac crest. Care must be taken to place the introducer greater than 1 cm from the fascial edge to avoid incorporation with the fascial stitch. A gentle curve can be placed in the introducer to facilitate proper positioning at the upper portions of the incision. The introducer device should be placed to its fullest extent. The obturator is withdrawn and a 19-G multiholed 12.5cm soaker catheter is then inserted through the sheath. The sheath can then be peeled away leaving the catheter sited in the pre-peritoneal space. The contralateral catheter is placed, starting adjacent to the first catheter (this will allow a single dressing to be used for both catheters). The catheters should be sutured to the skin and secured with a Tegaderm dressing. Following a bolus of 10ml 0.2% ropivacaine via both catheters, a continuous infusion of 0.2% ropivacaine is commenced using prefilled elastomeric pumps set to deliver 5ml/h (On-Q Pain Buster). Each pump contains 300ml and will therefore infuse for approximately 2.5 days. At this infusion rate plasma concentrations of ropivacaine are well below the level of toxicity and can be safely continued for up to 96 hours (24-25).
Figure 2: Images of pre-peritoneal catheter placement using the tunneled technique. The catheters are connected to two elastomeric infusion devices.
Watch video of pre-peritoneal catheter placement here
The peritoneal cavity is a single continuous space between the parietal peritoneum lining the abdominal wall and the visceral peritoneum enveloping the abdominal organs. Of mesodermal origin, it grows to a total area of approximately 1.8 m2 (almost equal to the body surface area of the skin) and provides a frictionless environment for movement of abdominal organs (26-27). The pre-peritoneal space refers to the ventral portion of the extraperitoneal space which is occupied by the parietal peritoneum internally and transversalis fascia externally (28). Within the pre-peritoneal space is a variable quantity of adipose tissue, loose connective tissue and membranous tissue (29). The parietal peritoneum is richly innervated by branches from somatic efferent and afferent nerves that also supply the muscles and skin respectively of the overlying body wall. Pain is elicited by mechanical, thermal or chemical stimulation of the nociceptors of the parietal peritoneum that are conveyed via Aδ and C primary afferents (30). The sensation is usually confined to one or two dermatomes for each area of peritoneum stimulated and is both lateralized and well localized. When the parietal peritoneum is irritated segmental muscles tend to contract reflexly causing guarding or even rigidity of the abdominal wall (31). The visceral peritoneum is innervated by branches of visceral afferent nerves which travel with the autonomic supply to underlying viscera. Stimulation of visceral afferents (stretch) mediates poorly localized sensations of discomfort (predominantly via the vagus and splanchnic nerves) and may also elicit profound reflex autonomic reactions involving vasomotor and cardiac changes (32). This is often associated with a strong emotional response (33).
Injection of radiopaque contrast media through a pre-peritoneal wound catheter has revealed that once injected it remains within the confines of the parietal peritoneum internally and muscular layers externally (14, 34). It is likely therefore that anaesthetic agents injected through a catheter into the pre-peritoneal space are able to act locally to block nociceptive afferents of the fascia of the abdominal muscles and the peritoneum. Both the fascia of the abdominal muscles and peritoneum are injured during laparotomy and contribute to postoperative pain and primary mechanical hyperalgesia (35). Indeed, animal studies indicate that deep tissues have a unique response to surgical incision and contribute greatly to pain at rest and opioid consumption (36). This may explain the lack of efficacy of subcutaneous wound infusions that block only cutaneous nociceptive afferents (8, 10, 11, 12, 37-39). A better understanding of the optimal placement of wound catheters may lead to improved analgesia and postoperative outcome (9). Indeed, in a comparative study of patients who underwent inguinal hernia repair, subfascial injection of lignocaine via a catheter resulted in significantly greater reduction in pain scores after coughing, mobilization and rest compared with subcutaneous catheter injection (40). Results of studies following prostatectomy, open nephrectomy, caesarian section and colorectal surgery further illustrate the need for deep catheter placement (14, 16, 34, 41).
The peritoneum is a metabolically active organ that responds to insult through a complex array of neuro-immuno-humoral cascades (42-45). Mesothelial cells and local peritoneal immune cells respond to peritoneal injury by secreting various mediators that are responsible for the local and systemic inflammatory response (42). The degree of activation of the neuro-immuno-humoral axis is likely to depend on the duration and degree of surgical challenge. Indeed, Theobald was able to perform hysterectomies under local anaesthesia and commented that the parietal peritoneum was fairly insensitive to manipulation including incision, pinching and pressure. However, ‘rough handling’ produced hypersensitivity necessitating general anaesthesia to continue with surgery (46).
Abdominal laparotomy induces peritoneal damage and the resulting peritoneal inflammatory response has several clinical consequences. Released proinflammatory cytokines can have a direct action on the vagus nerve and contribute to postoperative pain (47-56). The majority of peritoneal afferent fibres are normally unresponsive to noxious stimuli (‘silent nociceptors’) and only become sensitized in the presence of inflammation (57-58). Released inflammatory mediators decrease the threshold and increase the magnitude of the response to noxious stimulation in a phenomenon known as peripheral sensitization (59). Inflammatory sensitization underlies the perception of a normally innocuous stimulus as being painful and exaggerates the intensity of pain experienced during a painful stimulus (hyperalgesia). This exaggerated response in the presence of inflammation can be recognized in patients with acute peritonitis where gentle pressure on the abdomen elicits intense pain. Ropivacaine has been shown to suppress bradykinin and substance P mediated signaling and may be useful in the suppression of inflammation and prevention of postoperative hyperalgesia (60).
In addition to peripheral sensitization there is evidence that peritoneal injury induces changes within the central nervous system. Sugiyama et al have demonstrated that peritoneal incision is associated with increased spontaneous firing of wide dynamic range neurons in the rat spinal dorsal horn (61). The enhanced responsiveness of nociceptive neurons in the central nervous system has been termed central sensitization and is hypothesized to play a critical role in chronic somatic and visceral pain hypersensitivity (62-63). The mechanisms of central sensitization in various pain states have been reviewed recently (64-65). Central sensitization of dorsal horn neurons is thought to contribute to postoperative pain and mechanical hyperalgesia surrounding the wound (66). In addition, the extent of wound hyperalgesia in the days following surgery correlates with the incidence of chronic postsurgical pain (67). The use of prolonged intense multimodal analgesia during the perioperative period may reduce central sensitization and consequently post-surgical pain (68-69). This has been termed ‘preventative analgesia’ (70-72). This is a broader definition of pre-emptive analgesia that includes any perioperative analgesic regimen able to control incision induced sensitization (73). Interestingly, Beaussier et al reported that pain intensity did not increase after stopping the local anaesthetic wound infusion (14). They speculate this may relate to reduced central sensitization. This is in accordance with some recent data suggesting that the blockade of parietal afferents may reduce spinal dorsal horn neuron sensitization thereby providing postoperative analgesia that outlasts the duration of wound infusion (74). Furthermore, animal studies have shown that parietal pain may sensitize neurons in the spinal cord to visceral colonic pain (75-76). This sensitization most likely reflects convergence of afferent information from the gut and somatic system within the spinal cord (heterosynaptic facilitation) (77). The pre-peritoneal infusion of ropivacaine has recently been shown to prevent mechanical and visceral sensitivity following laparotomy in an animal model leading to the conclusion that both could be linked (78).
Time to ileus resolution after abdominal surgery is one of the most important factors contributing to the duration of hospital stay. Earlier resolution of postoperative ileus has been reported in studies of continuous local anaesthetic wound infusion (10, 12-14). A number of pathogenic mechanisms have been proposed for postoperative Ileus (79-80). Recent findings in a rodent model of postoperative ileus support the role of a local inflammatory reaction within the gut wall as a major causative factor (81). The clinical relevance of these findings in rodents has been confirmed in surgical specimens obtained from patients undergoing intestinal resection. In an elegant study Kalff et al demonstrated that surgical trauma is followed by activation of a network of macrophages that reside in the muscularis of the bowel wall (82). Subsequently there is upregulation in the production of interleukin (IL)-6, COX-2, TNF-α and iNOS. The release of these inflammatory mediators results in sluggish electrical and contractile responses of the muscularis that are the hallmark of paralytic ileus (83).
Intravenous lignocaine has been reported to speed the return of bowel function after surgery allowing for earlier rehabilitation and shorter duration of hospital stay. Inhibitory reflexes tend to be activated as soon as the parietal peritoneum is entered (84). By blocking these inhibitory reflexes, lignocaine can have a direct excitatory effect on intestinal smooth muscle. Other proposed mechanisms of enhanced bowel function relate to improved pain control, opioid sparing and reduced sympathetic tone (85-86). Additionally, as lignocaine is known to be anti-inflammatory, the mechanism of earlier return of bowel function may involve inhibition of the inflammatory response associated with surgical injury. The anti-inflammatory effects are thought to result from the interaction with G protein-coupled receptors of membrane proteins and lipids that regulate cell metabolic activity, migration, exocytosis and phagocycosis, (87-89).
As previously discussed the peritoneum responds to insult through a complex array of immunological and inflammatory cascades (42). There is clear evidence that specific inflammatory transcription factors, cytokine and chemokine upregulation and leukocyte recruitment have a direct inhibitory effect on the muscularis externa of the bowel (90-92). Intravenous lignocaine significantly attenuates plasma levels of complement and proinflammatory cytokines such as interleukin-6, interleukin-8 and interleukin-1 receptor antagonist at the end of colorectal surgery and up to 72 hours postoperatively (93-94). Lower levels of cytokine response are associated with the earliest return of bowel function (95). The anti-inflammatory effect of local anesthetics is prolonged and persists after serum levels have decreased (96-97). This may explain lignocaine’s effect on bowel function 36 h after stopping an infusion (98).
Experimental studies have shown that installation of local anaesthetics on the peritoneum can subdue the pronounced inflammatory response to an irritant (hydrochloric acid) (99). Furthermore, lignocaine applied directly to obstructed bowel serosa inhibits and reverses gut fluid losses and inflammation (100). Modification of the inflammatory response by local anesthetics when applied intraperitoneally may be responsible for reports of improved bowel motility in human studies (101-102). It is known that the pro-inflammatory response in the systemic circulation is a mere shadow of that occurring at the surgical site (103-105). This compartmentalization of the inflammatory response results in very high levels of cytokines in the peritoneal fluid in postoperative patients (106-107). The delivery of local anaesthetic drugs directly to the peritoneum via pre-peritoneal infusions may provide a useful mechanism to pharmacologically manipulate this inflammatory response (108). Ropivacaine has been shown to be an effective anti-inflammatory substance in an animal model of acute lung injury (109). The anti-inflammatory effect may be due to down-regulation of key chemotaxins. Interestingly, the attenuation of the inflammatory response occurred with intra-tracheal installation of ropivacaine. This may represent a local rather than systemic anti-inflammatory effect. It is possible that a similar anti-inflammatory mechanism occurs with pre-peritoneal infusions of ropivacaine. Fortunately, the anti-inflammatory effects of local anaesthetics do not appear to interfere with host defense mechanisms (110).
It has been hypothesized that a major part of the beneficial effects obtained from epidurally administered local anaesthetics is due to systemic absorption of the drug from the epidural space (111). The systemic absorption of local anaesthetics from the pre-peritoneal space may also be responsible for some of the reduced pain reported in patients undergoing bowel surgery (14). Although no data is available for ropivacaine, Tanelian and MacIver have established that the clinically effective pain relieving serum lignocaine concentration that is sufficient to reduce tonic injury discharge in both Aδ and C-fibres is 2-10µg/ml (112). At lower doses there is little or no effect on axonal transmission in peripheral nerves (113-114). This had led some to speculate that the primary sites of action for lignocaine are within the dorsal horn neurons of the spinal cord (115). Proposed mechanisms include possible involvement of neurokinin and N-methyl-D-aspartate (NMDA) linked systems as well as glycine linked systems (116-117). These spinal mechanisms may be responsible for the positive effect of lignocaine in animal models of visceral pain (118). It is feasible that some of the improved clinical outcome seen with pre-peritoneal ropivacaine infusion is via modulation of visceral signaling within the spinal cord. As visceral pain is often associated with a strong emotive response, inhibition of these spinal signals may attenuate the impact of major abdominal surgery on the patients overall sense of wellbeing. Additionally, it is known that chronic stimulation of spinal afferents from visceral organs may elicit pain, hyperalgesia and allodynia in the referred zones of the deep somatic tissues (skin, subcutaneous tissue, muscles and fascia) (119). Reduced visceral pain signaling within the spinal cord has been shown to reciprocally diminish cutaneous sensitization (120). As ropivacaine has recently been shown to reduce hyperalgesia by suppressing microglial activation in the dorsal horn it is possible that neuroimmune modulation within the central nervous system may be important (121).
Postoperative fatigue is a well recognized phenomenon that can accompany major colorectal surgery and is the subject of active research (122). Postoperative fatigue has been linked to the production of proinflammatory cytokines that act via the vagus and contribute to the ‘sickness response’ (123). Along with fatigue, the sickness response is characterized by difficulty concentrating, excessive sleep, decreased appetite and hyperalgesia (124). Higher degrees of postoperative fatigue are followed by worse emotional, physical and functional outcomes (125). Paddison et al found reports of fatigue to be significantly related to the IL-6, IL-10 and TNF-α concentrations present in the peritoneal cavity during the initial 24 hour period following colorectal surgery (126). Interventions that dampen the peritoneal response may be effective in reducing postoperative fatigue (42). Systemic dexamethasone has been shown to reduce postoperative fatigue after colonic surgery (127). It is unclear whether the effects observed were due to effects at a local or systemic level, but a significant reduction in peritoneal inflammatory cytokines would suggest that a local response was a major contributor. There is evidence that pre-peritoneal local anaesthetic infusion improves sleep quality and may reduce postoperative fatigue (14). Future research could be directed at the use of pre-peritoneal catheters to deliver anti-inflammatory drugs directly to the site of inflammatory cytokine production.
Thoracic epidural analgesia is regarded by some as the gold standard for open colorectal surgery (5). Thoracic epidural provides better analgesia when compared to more traditional methods in patients undergoing major open abdominal procedures (4). Additionally, epidural analgesia reduces the duration of ileus following colorectal surgery (79). However, when combined with fast-track recovery programs, thoracic epidural has not been found to reduce length of hospital stay compared with systemic opioids (128). In a recent audit of 600 sequential epidurals sited for postoperative analgesia, McLeod and colleagues demonstrated failure to provide good analgesia for the intended duration of the block in one-third of patients (7). Furthermore, there are serious complications specific to epidural analgesia (129). This has prompted some to change from epidural to multimodal analgesia for colorectal laparotomy. Chilvers et al ceased the routine use of epidural analgesia for colorectal laparotomy in favour of a six-drug multimodal regimen (MMR) comprising ketamine, clonidine, morphine, tramadol, paracetamol and a non-steroidal anti-inflammatory drug (130). They then audited the records of 54 patients who received the MMR and compared the findings to 59 previous patients who received epidural analgesia. They found that changing from epidural to the MMR produced comparable pain relief as well as reduction in complications, side effects, staff intervention and hospital stay (10 vs. 13 days). These findings indicate that there may be value in further researching multi-modal regimens’ (131-132). The addition of local anesthetic wound catheter techniques adds a further dimension to complement multimodal analgesic pharmacotherapy (133).
New and innovative techniques of local anaesthetic wound infusion for abdominal surgery have been reported. Blackford et al discuss a technique that involves the surgical placement of two fenestrated local anaesthetic wound catheters immediately superficial to the transversus abdominis muscle in subcostal upper abdominal incisions (134). They found a combination of a wound catheter (WC) and multimodal analgesic regimen (MMR) compared favourably with epidural analgesia. Pain scores were similar for both rest and with movement over the first three postoperative days. In addition, patients in the WC plus MMR had reduced anaesthetic preparation time (41 vs 54 min) as well as recovery ward time (90 vs 99 min). Cornish and Deacon describe their initial results using 16-G epidural catheters implanted in the posterior aspect of the rectus sheath for upper abdominal surgery (135). At the conclusion of surgery 20ml of local anaesthetic solution (bupivacaine 0.25% + 1:400,000 adrenalin) is injected through each catheter. Interestingly, in the first 6-12 hours postoperatively opioids were required for ‘visceral’ pain. Pain in the following 2-3 days postoperatively (‘somatic pain’) was completely controlled (visual analogue scale = 0/10). As both of these studies involved upper abdominal surgery it is unclear if these techniques will benefit patients having a midline laparotomy.
Padamanabhan et al found intermittent injection of local anesthetic (20ml 0.25% bupivacaine 8 hourly) into the rectus sheath after midline laparotomy did not reduce opioid requirement, pain score or peak expiratory flow (136). The time to resolution of ileus and discharge from hospital were not reported. As it is unclear if any or all of the patients had midline laparotomy for colorectal procedures it is difficult to compare this study with other studies using wound catheter infusions in colorectal surgery. Niraj et al compared the efficacy of subcostal transversus abdominis plane (TAP) catheters in patients undergoing elective open hepatobiliary or renal surgery to epidural analgesia (137). The TAP catheters (two 16-G epidural catheters) were inserted after identification of the transversus abdominis plane with an ultrasound probe. Local anaesthetic was injected intermittently (1mg/kg bupivacaine 0.375% 8 hourly). They found no significant advantage of epidural over subcostal transversus abdominis plane TAP catheter bolus for postoperative analgesia. As they had to resite nearly half of the TAP catheters the therapeutic application of this technique is unclear. Bharti et al describe a novel intra-abdominal approach to TAP block for postoperative analgesia in colorectal surgery (138). Using this single injection technique the authors found a significant reduction in 24 hour pain scores and morphine consumption. Time to return of bowel function and length of hospital stay were not reported. As this is a single injection method of TAP block, the clinical utility of this technique would appear to be limited to the first 24 hours postoperatively. Børglum et al describe a new four-point approach to ultrasound –guided TAP block for rescue analgesia in the post-anaesthesia unit for patients who had undergone major open or laparoscopic abdominal surgery (139). Four separate injections were used to anaesthetize the entire antero-lateral abdominal wall. All patients reported significant pain reduction after the blocks and reduced opioid consumption. As analgesia was short lived, lasting on average 6 hours, this new technique may more useful prior to the start of surgery. Analgesia could be continued postoperatively with a continuous local anaesthetic wound infusion technique (pre-peritoneal or subfascial catheter).
In summary, pre-peritoneal local anaesthetic infusions are simple, well tolerated and effective. They can be used in most patients and do not require specific postoperative supervision. Additionally unlike thoracic epidural analgesia they are easily maintained and do not require hourly assessment for signs of neurological damage (140). The technique could be considered as an interesting alternative to epidural analgesia (9, 18, 141). As with all new analgesic techniques several important questions remain unanswered and provide scope for future research. How long should the infusion be maintained after surgery? What is the optimal dose and volume of local anaesthetic that should be infused? Is there a difference in continuous vs. intermittent vs. patient controlled administration? Does the type of catheter used make a difference (multiholed soaker vs. epidural type catheter)? When used in combination with multimodal analgesia what combination of drugs should be used? Do local anaesthetic infusions impact on the incidence of chronic postsurgical pain? Will the addition of anti-inflammatory cytokines to local anaesthetic wound infusions confer benefit? (142).
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