Bupivacaine intermittent wound irrigation is an effective and cost­ reducing modality for postoperative analgesia after open cholecystectomy

Bupivacaine intermittent wound irrigation is an effective and cost­ reducing  modality for postoperative analgesia after open cholecystectomy

Ahmed Zeidan,a MD;  Hussein G El-Gohary,a MD; AshrafM Abd elkader,a MD; Mohamed Fouad,b MD

a) Department of General Surgery, Benha University, Benha, Egypt. b) Department of  Anesthesia, Benha University, Benha, Egypt.

Abstract

Objectives:To evaluate postoperative outcome of open cholecystectomy in patients receiving local   anesthetic  (LA)  wound   irrigation (WI)   for  postoperative (PO)   analgesia.

Patients & methods: The study included 40fomale patients with mean age of34.1±3.4 years. All surgeries were peiformed through Kocher's subcostal incision, during muscle cutting, the neurovascular bundle was identified and after peritoneal drainage and closure, an 8F neonatal feeding catheter with fashioned multiple pores was inserted partly between anterior abdominal wall muscles and partly under subcutaneous tissue directly on the neurovascular bundle. Patients were divided into: Control group (Group C) who received WI using 0.9% saline and study group (GroupS) who received 8-hourly WI using 20 ml ofbupivacaine  0.25%for 48 hours. Wound pain was assessed using 10-mm visual analogue scale (VAS). Duration of PO analgesia and frequency of requests and total dose of intravenous mepridine, time for first ambulation and oral intake were recorded. All patients were discharged after irrigation catheter removal on the morning of the 3rd PO day.

Results: All surgeries were completed uneventfully without complications within a mean operative time of 46.5±5.3 minutes. Patients who received LA irrigation showed significantly longer duration of analgesia with significantly lower frequency of requests and total dose of mepridine and lower cumulative VAS pain score compared to control group. Mean time tilllst ambulation and oral intake was significantly shorter in Group S compared to group C. Seven patients had postoperative nausea and/or vomiting (PONV), 4 in control and 3 in study group and only one patient in control group required stoppage of oral intake, but all patients responded well to antiemetic therapy.

Conclusion: Wound irrigation with bupivacaine significantly improved outcome of open

cholecystectomy and could be advocated for various open surgical procedures. The applied modality  was safe,  effective  and  cost reducing  with  significant opioid  sparing  effect.

Key words: Wound irrigation, bupivacaine, laparotomy.

Introduction:

Despite the widespread use oflaparoscopy, open surgery still constitutes one of the most frequent approaches for surgical management of various pathologies. The control of pain following these operations represents a major challenge as highly complex nociceptive pathways are involved especially if surgery required  extensive dissections, or  bowel

resection and anastomosis.l-3

Moreover, postoperative period is accompanied with neuroendocrine, metabolic and immune alteration which is caused by tissue damage, anesthesia, postoperative pain and psychological stress. Postoperative pain contributes to dysfunction of immune response as a result  of interaction between  central nervous  and   immune  system.     The

postoperatively activated hypotalamo-pituitary­ adrenocortical axis, sympathic and parasympathic nerve systems  are important modulators of immune response. According to bidirectional communication of immune and nervous system, appropriate postoperative pain management could affect immune response in postoperative period and helps to ameliorate the    postoperative  catabolic  state.4,5

However, post-laparotomy pain may not be amenable to pharmacological monotherapy, and systemic  application  of opiates  for pain relief  after open abdominal operations was found to be insufficient and intensive pain was noted  in  58%  of  patients, while  they  are

moving, and   in  26%--in  a  rest   state.s

Modem  analgesic  strategies involve  the combination of many  agents including parenteral opiates, non-steroidal anti­ inflammatory drugs, paracetamol and epidural infusion techniques. Unfortunately, there is no ideal analgesic regimen and all  current techniques have disadvantages in the form of important side-effects, cost, patient compliance, procedural complications  and  delays in discharge.6,7

For  patients who  had  laparotomy, it  is mandatory to provide the optimal pain control using  drugs  free of  side  effects  related to gastrointestinal motility or inducing respiratory complications, because this will hinder return of gastrointestinal motility thus delaying return to oral intake and subsequently  elongates the

duration of hospital stay.8-1o Wound perfusion

with local anesthetic is a promising modality for postoperative analgesia especially in cases requiring potent analgesics for a duration longer than the immediate postoperative period.11.12

Thus, the present prospective placebo­ controlled study aimed to evaluate the postoperative  outcome of open cholecystectomy in patients  receiving local anesthetic wound irrigation for postoperative analgesia.

Patients and methods:

The  present study was   conducted at Departments of General Surgery and Anesthesia, Benha University Hospital since Dec 2010 till May 2012. After approval of the study protocol by the Local Ethical Committee

and obtaining fully informed written patients' consent; 40 female patients assigned for open cholecystectomy were enrolled in the study.

Exclusion criteria included morbid obesity with body mass index>35 kg/m2, chronic pain,

liver  disease, psychological disorders and lactation. Also, patients with history of allergic disorders or development of adverse reactions to   local  anesthetics  were  excluded.

Enrolled  patients  underwent full history taking,  complete  physical  examination and radiological assessment. All surgeries  were conducted under  general anesthesia using cuffed endotracheal tube and were premedicated with midazolam  (2.5 mg) and atropine (0.5 mg). Also, ondansetrone 40 mg and dexamethasone 8 mg were given to prevent postoperative nausea and vomiting  (PONV) and combat laryngeal edema. Anesthesia was induced using propofol 2.5 mg/kg, cisatracurium 0.15 mg/kg and fentanyl 1Jlg/kg. After tracheal intubation, mechanical ventilation with 1:1 02:air was initiated  and adjusted to keep the end-tidal C02 tension in range of  30-35 mmHg. Anesthesia was maintained using  sevoflurane 1-1.5% and fentanyl1-2 Jlg/kglhr.At the end of procedure, neuromuscular  block reversal was given and patients were maintained  on 100% 02 at rate of 8 liters/min.

All  surgeries were  performed through

Kocher's subcostal incision, after skin incision was commenced, Figure(l) and during muscle cutting meticulous dissection was conducted for identification of the neurovascular bundle, Figure(l) which was marked  using a stitch loop outside the surgical field to be protected against injury. Then, cholecystectomy was conducted  and after peritoneal  drainage and closure, an 8F neonatal feeding catheter with fashioned multiple pores was inserted between internal oblique muscle and transversus abdominus as a catheter bed  and  external oblique was closed over the catheter so as to maintain some pores underneath of its sheath and others were out to irrigate the subcutaneous tissue, Figure(3).  The catheter was tested for patency using 20 cc of saline injected through it. Then subcutaneous tissue and sldn  were closed.Each of drainage and irrigation catheters was extracted through watertight separate stab

for each away from the main wound line, Figure(4). Irrigation catheter was fixed to abdominal wall  allowing free  end for application of irrigation syringe.

Patients were  randomly, using  sealed envelops, divided into two groups according to irrigation fluid:Control group (Group C) received wound irrigation using 0.9% saline and study group (GroupS) received intermittent wound irrigation every 8 hours for 48 hours using 20 ml of bupivacaine 0.25%. Once patients were completely recovered, wound was irrigated for the first time with assigned solution. Wound pain was assessed hourly using 10-m:m visual analogue scale (VAS)

Figure (1): Skin incision and dissection of subcutaneous tissue.

Figure (3): Catheter was inserted beneath muscular layers (arrow).

Statistical analysis:

Obtained data were presented as m.ean±SD, ranges, numbers and ratios. Results were analyzed  using Wilcoxon's ranked test for unrelated data (Z-test) and Chi-square test (X2

test) for numerical data. Statistical analysis was conducted using the SPSS (Version 15,

2006) for Windows statistical package.P value

<0.05 was considered statistically significant.

starting after patients transfer to post-anesthetic care unit for four hours and then four-hourly till48 hours and cumulative VAS pain score was calculated.  Duration  of analgesia  was defined as the time lapse since first wound inigation tillrequest of rescue analgesia.Rescue analgesia  for both groups was provided as intravenous mepridine 50 mg on request or at VAS. The frequency ofPONV, side effects or complications occurring with the first 48 postoperative hours was reported. Time for first  ambulation and oral  intake  was also recorded. All patients were discharged after irrigation catheter removal on the morning of the 3rd postoperative day.

Figure (2): Dissection and identification of the neurovascular bundle as shown elevated by the forceps.

Figure(4): Catheter was extracted out of the wound through a separate stab away from that used for the bed drainage.

Results:

The study included 40 female patients with mean age of 34.1±3.4; range: 26-43 years. Thirty-one patients (77.5%) were ASA grade I and 9 patients (22.5%) were ASA grade D. All surgeries were completed uneventfully without intraoperative complications within a mean operative time of 46.5±5.3; range:35.8-

55 minutes. Patients' details and operative

times were shown in Table(l). There was a non-significant (p>0.05) difference between studied patients as regards the age, weight, height, body mass index (BMI), ASA grade and duration of surgery. Baseline measures of SAP,HR, RR and Sp02 showed non-significant (p>0.05) difference between both groups with non-significant change recorded at end of PO

24-hrs compared to baseline measures and between both groups, Table(2).

Patients  who received  local  anesthetic

irrigation showed  significantly longer, (Z=3.926, p<O.OOl) duration ofPO analgesia compared to those who received placebo, Figure(5). Throughout 48-hr PO, 12 patients (60%) in group S requested rescue analgesia once, 7 patients (35%) requested it twice and only one patient (5%) requested it thrice.While in group C, 12 patients (60%) requested rescue analgesia twice and 8 patients (40%) requested it thrice with significantly or-=-7.807, p<O.Ol) lower frequency of number of requests of rescue analgesia in study group compared to

control group. Mean cumulative VAS pain score, recorded throughout 48 hours after surgery, was significantly lower in group S compared to group C, (Z=3.735, p<O.OOl). Moreover, total dose of mepridine consumed throughout 48 hours was significantly lower, (Z=4.359, p<O.OOl) in groupS compared to group C, Table(3).

Mean   time   till   1st   ambulation  was

significantly shorter, (Z=2.070, p=0.038) in groupS compared to group C, Figure(6). Also, mean time till 1st oral fluid intake was significantly, (Z=2.397, p=0.017) shorter in group S compared to group C, Figure(7). Only

7 patients had PONV, 4 in control and 3 in study group  with non-significant (p>0.05) difference between both groups. One patient in control group required stoppage of oral intake, but all patients responded well to antiemetic  therapy. No patient developed allergic manifestations to bupivacaine and all patients were discharged after removal of the irrigation catheter.

Table (1): Patients' data and duration of surgery.

Data are presented as mean±SD, ratio and ranges are in parenthesis      BMI: Body mass index.

Table (2): Patients' vital data recorded at end of JS 124hours after surgery compared to their baseUne data.

Data are presented as mean±SD.

SAP: Systolic arterial blood pressure.                          Sp02: Partial arterial oxygen saturation.

Data are presented as mean±SD & numbers,· ranges and percentages are in parenthesis.

32

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Figure (5): Mean (±SD) duration of postoperative analgesia.

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Figure (7): Mean (±SD) duration till first oral intake.

Discussion:

Considering the primary outcome of the current study as the efficacy oflocal anesthetic wound irrigation as a modality for provision

of postoperative analgesia; patients received i:rrigation showed significantly lower pain VAS scores with longer duration of postoperative analgesia and lower consumption of rescue analgesia. These data illustrated the beneficial effect of such modality for pain management and supported that previously reported in literature.

Bamigboye & Hofmeyrl3 searched the

Cochrane Pregnancy and Childbirth Group's Trials Register and found women who had Caesarean section performed under regional analgesia and had wound infiltration and women  under  general  anesthesia,  with Caesarean section wound infiltration and peritoneal spraying with anesthetic had a decreaseinmotphine consumption at 24 homs

compared to placebo.Sostaric et al.l4 evaluated

the analgesic effect of catheter continuous infusion of local anesthetic for patients who hadPort Access heart surgecy with the catheter placed in the surgical wOUDd at the end of the operation and reported that such analgesic modality provided acceptable level of postoperative paincontrolandcatheter insertion in surgical incision and application of local anesthetic through it does not increase the risk for wolDl.d infection nor interfere with wound healing. Also, Gottschalk & GottschaJk:IS

reported that continuous wound infusion of local anesthetics is able to reducepostoperative opioid requirements and results in decreased pain scores.

Heil et aJ.l6 found ultrasound-guided tnmsversus abdominis planeperineuralcatheter insertion and subsequent management of ambulatory local anesthetic infusions after inguinal hernia repair provided minimal pain during the forty-eight hours of infusion without the need for any supplemental opioid anaJgesics, high satisfaction with postoperative analgesia, and no infusion-related complications.Wang et al.l7 reported that local anesthesia infusion at the fascial plane after laparotomy provided effective analgesia, significaDtly decJ:eased consumptionof opioids, and improved patient recovery through significantly earlier independent mobilization, return of bowel function and reduced post­ operative ileus. Aizenberg et al.l8 found posroperative wound irrigation wi1h 0.1-0.2% solution ofropivacaine in combination with non-steroidal anti-inflammatory drugs (NSAIDs) is effective analgesic modality after surgical correction of scoliotic spinal deformities with reduction of vomiting after surgery and the best effect is achieved with the constant introduction of 0.2% solution of ropivacaine.

On contrary to the results of the current study, Talbot et aJ.l9 tried to determine the influence of anesthetic of axillary drains on

postoperative pain  during the  first   24  h following a modified Patey mastectomy versus placebo irrigation and  found  no statistical differences in morphine requirements or pain scores  between  the   two   groups,  nor supplemental analgesic consumption and concluded that bupivacaine used in this manner does  not   appear  to   offer an  effective contribution to postoperative analgesia. This discrepant result  could  be attributed to the more extensive type of surgery requiring tissue dissections and sacrificing of multiple sensory nerves  with the resultant  of release of large number of nociceptive stimuli, secondly, such type of surgery limits movement of shoulder joint which must be moved for daily activities and to guard against stiffuess and this in virtue is a painful movement which aggravates wound pain sensation, thirdly,  through  the current study the neurovascular bundle was clearly dissected through a clean new wound prior to proper surgical interference to protect it against trauma and  fourthly, the  site  of  catheter insertion being partly underneath  of muscles and partly under the skin so irrigation included both muscles and skin nerves and was directly on  the  neurovascular bundle blocking it.

In support of the obtained results, Singh et

al.20,21 found  continuous infusion of 0.5%

Marcain  at the iliac crest bone graft harvest site significantly reduced chronic dysesthesias with significantly better overall satisfaction, number of painful days per month, and VAS scores at 4 years with no  long-term complications. Sidiropoulou et al.22 compared the analgesic  efficacy  of continuous wound infiltration of  local anesthetic versus paravertebral analgesia after mastectomy with axillary dissection  and reported  that despite the better outcome of paravertebral analgesia during the first postoperative hours, continuous wound irrigation provided lower pain scores and lower  frequency of  painful  restricted movement  at 16 and 24 hours after surgery.

As a further support for the feasibility and

effectiveness of local wound irrigation using local anesthetic, Zhirkova et al.12 and Zhirkova

& Marganiia,23 evaluated the effectiveness of postoperative analgesia in neonates using local anesthetic wound irrigation as rated by CRIES postoperative pain control scale, monitoring

of skin conductance, cardiointervalogram and hormone level control in the blood and found the use of catheter for continuous postoperative analgesia provides effective level of analgesia in newborns,  which  is comparable with the introduction of  opioid  analgesics without postoperative complications and recommended this method  of analgesia for  postoperative analgesia in newborns, especially during major surgeries. Panaro et al.24 reported that surgical wound infusion with ropivacaine was safe and seemed to improve pain relief and accelerate recovery and discharge, reducing the overall costs of care after laparoscopic living donor nephrectomy.

It could be concluded that wound irrigation with bupivacaine  significantly improved  the outcome of open cholecystectomy and could be advocated for various open  surgical procedures. Additionally, the applied modality was safe,  effective and cost reducing with significant opioid sparing effect.

References:

1- Mann C, Pouzeratte Y, Boccara G, Peccoux C, Vergne C, Brunat G, Domergue J, Millat B, Colson P: Comparison  of intravenous or epidural patient-controlled  analgesia in the elderly after major abdominal surgery. Anesthesiology 2000;  92(2):  433-441.

2- Rimaitis K, Marchertiene I, Pavalkis D: Comparison  of two different  methods of analgesia. Postoperative course after colorectal cancer surgery. Medicina (Kaunas)  2003;  39(2):  129-137.

3- Schumann R, Shikora S, Weiss JM, Wurm

H, Strassels S, Carr DB: A comparison of multimodal perioperative analgesia to epidural  pain  management after  gastric bypass surgery. Anesth Analg 2003; 96(2):

469-474.

4- Golubovic S, Golubovic V, Sotosek­ Tokmadzic V, Sustic A, Petkovic M, Bacic D, Mrakovcic-Sutic I: The proposed mechanism of action during different pain management  techniques on expression  of cytolytic molecule perforin in patients after colorectal cancer surgery. Med Hypotheses

2011; 76(3): 450-452.

5- Potapov AL, Kobeliatski1lulu: Opiates do not guarantee an adequate analgesia after

large-volume open  operations on the abdominal cavity organs. Klin Khir 2011; (8): 28-31.

6- Nikoda  VV, Maiachkin RB, Bondarenko AV: Efficacy and safety oflomoxicam in an early postoperative period.  Ter Arkh

2007; 79(8): 28-33.

7- Beaussier M, El'ayoubi H, Rollin M, Pare Y, Atchabahian A, Chanques G, Capdevila X, Lienhart A, Jaber S: Parietal analgesia decreases postoperative diaphragm dysfunction induced by abdonrinal surgery: A physiologic study. Reg Anesth Pain Med

2009; 34(5): 393-397.

8- Inanoglu K, Ozcengiz D, Gunes Y, Unlugenc H, Isik  G: Epidural ropivacaine versus ropivacaine plus tramadol in postoperative analgesia in children  undergoing major abdominal  surgery: A  comparison. J Anesth 2010; 24(5): 700-704.

9- Nicolau AE, Merlan V, Grecu I, Nicolau M,  Micu  B:  Multimodal analgesia in elective laparoscopic cholecystectomy. A double-blind randomized controlled trial. Chirurgia 2008;  103(5):  547-551.

10-Borisov DB,  Levin  AV,  Uvarov DN, Kapanadze LG, Nedashkovskii' EV: Balanced postoperative analgesia in abdominal surgery: Efficiency of  the combined use of epidural block and non­ opioid analgesics. Anesteziol Reanimatol

2009; (2): 35-37.

11-Chan SK, Lai PB,LiPT, Wong J, Karmakar MK, Lee KF, Gin T: The analgesic efficacy of continuous wound  instillation with ropivacaine after  open  hepatic  surgery. Anaesthesia  2010;  65(12): 1180-1186.

12-Zhirkova IuV, Stepanenko SM, Kucherov lUI: Postoperative  analgesia of newborns using  administered through    catheter  of permanent action. Anesteziol Reanimatol

2011; (1): 55-58.

13-Bamigboye AA,  Hofmeyr GJ:    Local anaesthetic wound infiltration and abdominal nerves block during caesarean section for postoperative pain relief. Cochrane Database Syst Rev 2009; (3): CD006954.

14-Sostaric M, Gersak B, Novak:-Jankovic V: The analgesic efficacy of local anesthetics for the incisional administration following

port  access  heart  surgery: Bupivacaine versus  ropivacaine. Heart Surg Forum

2010; 13(2): 96-100.

15-Gottschalk A, Gottschalk  A: Continuous wound infusion of local  anesthetics: Importance in postoperative pain therapy. Anaesthesist  2010;  59{12): 1076-1082.

16-Heil  JW, Ilfeld BM, Loland  VJ, Sandhu

NS, Mariano ER: Ultrasound-guided transversus abdominis plane catheters and ambulatory perineural infusions for outpatient inguinal hernia repair. Reg Anesth Pain Med 2010; 35(6): 556-558.

17-Wang  LW, Wong SW, Crowe  PJ, Khor KE, Jastrzab G, Parasyn AD, Walsh WR: Wound infusion with local anaesthesia after laparotomy: A randomized controlled trial. ANZ  J Surg  2010; 80(11): 794-801.

18-Ai'zenberg VL, Ul'rikh GE, Ukolov Klu, Zabolotskii' DV, Ivanov MD, Malashenko NS: Methods of analgesia in children after surgical correction of the scoliotic spinal deformities. Anesteziol Reanimatol2011; (1):59-62.

19-Talbot H, Hutchinson  SP, Edbrooke  DL, Wrench I, Kohlhardt SR: Evaluation of a local anaesthesia regimen following mastectomy. Anaesthesia 2004; 59(7): 664-

667.

20-Singh K, Samartzis D, Strom J, Manning D, Campbell-Hupp  M, Wetzel FT, Gupta P, Phillips FM:A prospective, randomized, double-blind study evaluating the efficacy of postoperative continuous local anesthetic infusion  at the iliac crest bone graft site after spinal  arthrodesis. Spine (Phila Pa

1976).  2005;  30(22):  2477-2483.

21-Singh  K, Phillips  FM, Kuo E, Campbell M: A prospective, randomized, double­ blind study of the efficacy of postoperative continuous local anesthetic infusion at the iliac crest bone graft site after posterior spinal arthrodesis: A minimum  of 4-year follow-up.  Spine (Phila Pa 1976). 2007;

32(25): 2790-2796.

22-Sidiropoulou T, Buonomo 0, Fabbi E, Silvi MB, Kostopanagiotou G, Sabato AF, Dauri M:A prospective comparison of continuous wound infiltration with ropivacaine versus single-injection paravertebral block after modified radical mastectomy. Anesth Analg