Pre-/Intra-operative Interventions - ESRA
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Laparoscopic Cholecystectomy 2017

Pre-/Intra-operative Interventions

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • Two studies showed a significant reduction in pain scores within the first 2 h after operation, compared with placebo, when an IV paracetamol infusion was administered before operation (Choudhuri 2011, LoE 2, n=80; Salihoglu 2009, LoE 1, n=40)
  • Intra-operative IV paracetamol (administered 10 min after induction) reduced pain up to 5 h after operation when compared with placebo (n=30) (Gousheh 2013; LoE 1)
  • Pre- and postoperative (for 24 h) IV paracetamol infusions reduced pain scores compared with IV dexmedetomidine over the first 24 h after operation (n=78) (Swaika 2013; LoE 2). Both groups had adequate analgesia, but IV paracetamol was associated with significantly less sedation when compared with dexmedetomidine infusions
  • When pre- and postoperative IV paracetamol was compared with oral paracetamol, there was no significant difference in pain scores or opioid consumption (n=60) (Plunkett 2017, LoE 1)
  • One study showed no difference between pre-operative IV paracetamol and IV ketorolac in terms of pain scores or analgesic use, but included no control group (n=98) (Medina-Vera 2017; LoE 1)

PROSPECT Recommendations

  • Pre-operative oral paracetamol is recommended for routine use (Grade A) based on analgesic efficacy in several studies in this and the previous review (LoE 1 and 2)
  • If not given pre-operatively, intra-operative IV paracetamol is recommended for routine use (Grade A, LoE 1)
  • The previous review recommended only postoperative paracetamol, but this review extends this recommendation to the pre-/intra-operative period

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • Five studies examined the use of pre-operative NSAIDs/COX-2-selective inhibitors compared with placebo/control, showing either reduced pain, analgesic requirement, or both (Sandhu 2011, LoE 1, n=119; Papadima 2007, LoE 2, n=76; Puura 2006, LoE 1, n=72; Ahiskalioglu 2017, LoE 2, n=65; Shuying 2014, LoE 1, n=113)
  • One study found reduced pain scores and tramadol consumption with pre-incision IM diclofenac or transdermal diclofenac 6 h before the operation compared with pre-operative oral diclofenac (n=90) (Ural 2014; LoE 1)
  • One study found reduced pain scores and opioid consumption in the early postoperative period with lornoxicam compared with tenoxicam (n=57) (Kocaayan 2007, LoE 1)
  • In one study, intra-operative IV dexketoprofen reduced opioid consumption but not pain scores compared with IV diclofenac (n=60) (Anil 2016; LoE 2)
  • IV parecoxib reduced pain scores and rescue analgesic consumption compared with control, in a three-arm study comparing intra-operative SC bupivacaine, IV parecoxib and control (n=180) (Lin 2015; LoE 2)
  • One study showed no difference between pre-operative IV paracetamol and IV ketorolac in terms of pain scores or analgesic use, but included no control group (n=98) (Medina-Vera 2017; LoE 1)

PROSPECT Recommendations  

  • Pre-operative oral NSAIDs/COX-2-selective inhibitors are recommended for routine use (Grade A) based on several studies showing analgesic efficacy in this and the previous review (LoE 1 and 2)
  • If not given pre-operatively, intra-operative IV NSAIDs/COX-2-selective inhibitors are recommended for routine use (Grade B, LoE 2)
  • The previous review recommended the use of COX-2-selective inhibitors before operation (Grade B)
  • The previous review recommended the use of intra-operative NSAIDs and COX-2-selective inhibitors, at the end of surgery (Grade D)

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • Seven studies have examined the effect of preoperative dexamethasone. All showed analgesic effectiveness for up to 48 h after operation (Fukami 2009, LoE 2, n=80; Sánchez-Rodríguez 2010, LoE 2, n=210; Sistla 2009, LoE 1, n=70; Murphy 2011, LoE 1, n=115; Ryu 2013, LoE 1, n=72; Lim 2011, LoE 2, n=120; Lee 2017, LoE 2, n=380)
  • Furthermore, five of those studies have demonstrated a significant reduction in rates of nausea and vomiting (Fukami 2009, LoE 2, n=80; Sánchez-Rodríguez 2010, LoE 2, n=210; Sistla 2009, LoE 1, n=70; Murphy 2011, LoE 1, n=115; Lee 2017, LoE 2, n=380)
  • Dexamethasone with rofecoxib, ondansetron, and metoclopramide reduced the highest pain felt (p=0.032) and pain on arrival to ward (p=0.003) (Antonetti 2007; LoE 2, n=205). The extent of the effect is unknown as the control group did not receive postoperative NSAID

PROSPECT Recommendations  

  • Pre-operative dexamethasone is recommended for routine use (Grade A) based on evidence of analgesic and anti-emetic effects (LoE 1 and 2)
  • The previous review recommended dexamethasone use with Grade B evidence

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results

Arguments for…

  • Pre-operative gabapentoids were shown to be effective in reducing pain scores and/or analgesic requirements compared with placebo/control in 8 of 11 studies (Peng 2010, LoE 1, n= 142; Balaban 2012, LoE 2, n=90; Agarwal 2008, LoE 1, n=56; Sarakatsianou 2013, LoE 1, n=40; Choubsaz 2017, LoE 1, n=168; Gupta 2017, LoE 1, n=90; Mishra 2016, LoE 2, n=90; Anand 2017, LoE 1, n=60)
    • Three studies showed no significant difference between pre-operative gabapentinoids and placebo in terms of pain scores (Chang 2009, LoE 1, n=77; Bekawi 2014, LoE 1, n=90; Gurunathan 2016, LoE 1, n=100), but Bekawi 2014 showed a reduction in analgesic use with gapapentinoids
  • In one three-arm study, both pre-operative pregabalin 150 mg and gabapentin 600 mg were more effective for reducing pain than diclofenac 100 mg (n=107) (Pandey 2014, LoE 1)
  • In one three-arm study, both pre-operative pregabalin 150 mg and 300 mg were more effective for reducing pain than paracetamol 1 g (n=75) (Esmat 2015, LoE 2)
  • One study found no significant difference in pain scores or analgesic consumption between pregabalin 150 mg and gabapentin 300 mg (n=50) (Kochhar 2017, LoE 1)
  • In one study, pre-operative pregabalin plus ibuprofen was more effective for reducing pain scores than pregabalin alone (n=58) (Karaca 2017, LoE 1)

PROSPECT Recommendations  

  • Preoperative gabapentinoids are not recommended for routine use but may be considered if ‘basic’ analgesia is not possible (Grade D)
  • Although several studies have reported reduced postoperative opioid requirements (LoE 1 and 2) with pre-operative gabapentinoids, they may not add to the effectiveness of the ‘basic’ analgesic technique of paracetamol, NSAID/COX-2-selective inhibitors, and surgical site infiltration
  • Also, the optimal dose is unknown, and there is a need to balance analgesic benefits with potential adverse effects such as increased potential for sedation
  • The previous review recommended pre-operative gabapentinoids (Grade B)

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results

Arguments against…

  • Pre- and postoperative (for 24 h) IV dexmedetomidine infusions increased pain scores compared with IV paracetamol over the first 24 h after operation (n=78) (Swaika 2013; LoE 2). Both groups had adequate analgesia, but IV paracetamol was associated with significantly less sedation when compared with dexmedetomidine infusions
  • Clonidine administered before operation did not significantly reduce pain scores but reduced analgesic requirement compared with placebo (n=50) (Singh 2011; LoE 2)

PROSPECT Recommendations  

  • Alpha-2 agonists, such as dexmedetomidine and clonidine, are not recommended because of limited evidence and potential adverse effects (Grade D)
  • Clonidine was recommended in the last review despite minimal evidence

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results 

Arguments against…

  • One paper examined the use of pre-incision ketamine with and without pre-induction diclofenac, showing that pre-incision ketamine alone was not superior to placebo but was effective in combination with diclofenac (n=80) (Nesek-Adam 2012; LoE 1)
  • Comparison between the combination of pre-operative gabapentin, ketamine, lornoxicam, and local ropivacaine, each of these drugs alone, and placebo showed no benefit of ketamine alone (n=148) (Kotsovolis 2015; LoE 1)
  • Five of nine studies showed no significant benefit in reducing postoperative pain with intra-operative ketamine infusion (López-Álvarez 2012, LoE 1, n=60; Leal 2013, LoE 1, n=40; Park 2010, LoE 1, n=65; Lee 2014, LoE 1, n=60 [except in first 15 minutes]; Moro 2017, LoE 1, n=119)
    • Only one of those studies showing no effect on pain scores with ketamine demonstrated a reduction in opioid requirement (n=60) (Lee 2014; LoE 1)
    • Intra-operative ketamine reduced postoperative pain and opioid requirement in four studies (Karcioglu 2013, LoE 1, n=37; Singh 2013, LoE 1, n=80; Choi 2016, LoE 1, n=54; Miziara 2016, LoE 1, n=42)

PROSPECT Recommendations  

  • Ketamine has shown mixed results regarding reduction of pain and analgesic requirement, and overall it is not recommended (Grade D, LoE 4). Additionally, there are concerns about adverse effects such as hallucinations
  • The previous review did not recommend ketamine use before or during operation (Grade D)

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results

Arguments for…

  • Two studies examined pre-operative magnesium infusion compared with saline control, one showing a reduction in pain up to 24 h (Olgun 2012, LoE 2, n=60) and the other a reduction for the first 3 h only (Bačak Kocman 2013, LoE 2, n=60). Both showed a reduction in analgesic requirement with magnesium compared with saline.
  • Intra-operative magnesium showed reduced pain scores within the first 24 h when compared with placebo in two studies. Both studies showed reduced postoperative opioid requirements (Mentes 2008, LoE 2, n=83; Saadawy 2010, LoE 1, n=120)

PROSPECT Recommendations  

  • Magnesium is not recommended (Grade D) despite some evidence of analgesic effect (LoE 1). Magnesium during operation may cause adverse effects such as potentiation of neuromuscular blocking agents and increasing the incidence of residual muscle paralysis
  • The previous review did not recommend magnesium use before or during operation Grade D

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results 

Arguments for…

  • Five studies examined the use of peri-operative lidocaine infusion, and all (Lauwick 2008, LoE 1, n=49; Song 2017, LoE 1, n=73; Bakan 2015, LoE 1, n=85; Jain 2015, LoE 1, n=60) but one (Ortiz 2016, LoE 1, n=43) showed reduced postoperative pain scores and/or analgesic requirement compared with controls

PROSPECT Recommendations  

  • IV lidocaine infusions are not recommended (Grade D), despite evidence of analgesic benefit (LoE 1), owing to the need for close monitoring and the possibility of overdose
  • IV lidocaine infusion was not recommended in the last review (Grade D)

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results 

Arguments for…

  • Intra-operative esmolol infusion did not affect postoperative pain but reduced fentanyl use compared with controls (Lee 2014, LoE 1, n=60; Collard 2007, LoE 1, n=85)
  • One study showed reduced pain scores and analgesic requirement with intra-operative esmolol compared with placebo (Dhir 2015; LoE 2)

PROSPECT Recommendations  

  • Esmolol infusions are not recommended (Grade D), despite evidence of analgesic benefit (LoE 1 and 2), owing to the need for close monitoring and the possibility of overdose
  • The previous review made no recommendation regarding esmolol infusions

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • Port-site infiltration with ropivacaine was associated with reduced pain scores at 1 h, 24 h and at discharge, and reduced total analgesic requirement, compared with placebo (n=72) (Liu 2009; LoE 2)
  • One study examined infusion of ropivacaine into the wound for 24 h. The ropivacaine group reported less pain during cough in the PACU and at 4 h after operation compared with placebo (Fassoulaki 2016, LoE 1, n=110)
  • One study compared local tramadol infiltration into wounds versus IV tramadol and found no significant difference in pain scores beyond 30 min but there was a reduction in the use of rescue analgesia with the local tramadol group (n=70) (Matkap 2011; LoE 2)
  • One of two studies found analgesic benefits with the combination of port-site infiltration of LA plus intraperitoneal LA:
    • One study showed a significant reduction in parietal pain scores and total fentanyl use with port-site LA versus placebo. The combination of port-site LA and intraperitoneal LA was associated with a significant reduction in parietal, visceral and shoulder pain scores as well as total fentanyl use compared with placebo (n=80) (Cha 2012; LoE 1)
    • Another study compared placebo with a combination of intraperitoneal LA and port-site LA, demonstrating no difference in pain scores or analgesic requirements (n=78) (Hilvering 2011; LoE 1)

PROSPECT Recommendations  

  • Port site LA is recommended, preferably administered before incision, using a long-acting LA to prolong its effect (Grade A), based on evidence of analgesic benefit (LoE 1 and 2)
  • The previous review recommended wound infiltration with long-acting LA (Grade A)

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • Nine of twelve studies found a reduction in pain scores with transversus abdominis plane (TAP) or oblique subcostal TAP (OSTAP) blocks compared with placebo or controls:
  • Two of four studies showed a benefit of TAP blocks compared with LA infiltration into the wounds (Elamin 2015, LoE 1, n=80; Tolchard 2012, LoE 1, n=43), with two showing no consistent benefit (Ortiz 2012, LoE 2, n=74; Bava 2016, LoE 1, n=42)
  • One study showed a reduction in pain scores with 30 mL USG TAP block (50 mg bupivacaine + 20 mL saline solution) versus 20 mL USG TAP block (50 mg bupivacaine + 10 mL saline solution) (Sahin 2017, LoE 1, n=60)
  • One study found a reduction in pain scores in the immediate postoperative period for USG TAP block with 0.375% ropivacaine versus 0.25% bupivacaine (Sinha 2016, LoE 1, n=60)
  • One study found that ultrasound-guided field block was associated with reduced pain and analgesic requirement compared with port site infiltration (Saxena 2016; LoE 1, n=80)

PROSPECT Recommendations

  • TAP or OSTAP blocks are not recommended for routine use (Grade D), despite several studies reporting reduced postoperative opioid requirements and pain scores (LoE 1 and 2), as they may not add benefit beyond the ‘basic’ analgesic protocol. However, they may be considered if ‘basic’ analgesia is not possible
  • The previous review did not recommend TAP or OSTAP blocks as no evidence was identified

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

Arguments against…

  • There were considerable differences in the methods of LA instillation including the location (sub-diaphragmatic, gallbladder bed, or both, and with or without wound infiltration) and timing (before or after the removal of the gallbladder) between the trials. Various IP LA were used, but bupivacaine was the most common.
  • A recent Cochrane review (Gurusamy 2014) showed only a marginal effect from many poor-quality studies of IP LA
  • Two studies found reduced pain scores with PS infiltration compared with IPLA (El-Labban 2011, LoE 1, n=189; Altuntas 2016, LoE 2, n=90)
  • One study found that IV tramadol, but not IP tramadol, reduced pain scores compared with control, but only in the immediate postoperative period (Akinci 2008, LoE 1, n=61)
  • One study found that rectal sheath block reduced pain scores compared with IP LA (Gupta 2016, LoE 2, n=75)

PROSPECT Recommendations  

  • IP LA instillation is not recommended (Grade D), despite a majority of studies reporting reduced postoperative opioid requirements and pain scores (LoE 1), as it may not add benefit beyond the ‘basic’ analgesic protocol
  • The previous review recommended IP LA for wound pain (Grade A)
  • The addition of IP LA with port site local infiltration could potentiate LA toxicity. If IP LA is used, care should be taken to control the maximum dosage while still giving adequate port site LA

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • One study examined the effect of paravertebral block given before induction compared with no block, showing no difference in pain scores but lower morphine requirement with the block (Agarwal 2012, LoE 1, n=50). However, the study is difficult to interpret given that there was no mention if LA was used in the wounds
  • Another study found an analgesic benefit of pre- versus postoperative paravertebral blocks (Naja 2011, LoE 1, n=57)

PROSPECT Recommendations  

  • Regional anaesthesia techniques such as epidural anaesthesia, paravertebral block, intrathecal opioids, and rectus sheath block are not recommended because of limited, small trial evidence and potential for complications or failure of anaesthetic technique (Grade D)

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • Two studies examined combined spinal/epidural anaesthesia (CSEA) versus general anaesthesia. The pain was less for the CSEA group on discharge (Ross 2013, LoE 1, n=20) and up to 24 h (Donmez 2017, LoE 2, n=49)

PROSPECT Recommendations  

  • Regional anaesthesia techniques such as epidural anaesthesia, paravertebral block, intrathecal opioids, and rectus sheath block are not recommended because of limited small trial evidence and potential for complications or failure of anaesthetic technique (Grade D)
  • Epidural anaesthesia is also counterintuitive in the ambulatory setting

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results

Arguments for…

  • Thirteen studies examined the effect of low pressure pneumoperitoneum, and ten found a benefit for reduction of pain scores and/or shoulder tip pain with lower (7–<12 mm Hg) versus standard/higher pressures (12–16 mm Hg) (Singla 2014, LoE 2, n=100; Yasir 2012, LoE 2, n=100; Kanwer 2009, LoE 1, n=55; Esmat 2006, LoE 2, n=109; Joshipura 2009, LoE 1, n=26; Sattar 2015, LoE 2, n=180; Kandil 2010, LoE 2, n=100; Bhattacharjee 2017, LoE 1, n=80; Kim 2017, LoE 2, n=54; Ko-iam 2016, LoE 1, n=120). Most of these studies also found a reduction in analgesic consumption with lower versus higher pressures
    • Three studies found no significant difference in pain scores or analgesic consumption (Celik 2010, LoE 2, n=60; Sandhu 2009, LoE 1, n=138; Chok 2006, LoE 2, n=40)

PROSPECT Recommendations  

  • Low-pressure pneumoperitoneum (10–12 mm Hg) is recommended if surgically possible (Grade A) based on evidence of analgesic benefit in a majority of studies (LoE 1 and 2)
  • The previous review recommended low-pressure pneumoperitoneum (Grade A)

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments for…

  • One of three studies demonstrated lower pain scores with saline lavage compared with controls (Bala 2015, LoE 1, n=60), and two studies demonstrated lower analgesic requirements in the saline lavage group (Barthelsson 2015, LoE 1, n=71; Bala 2015, LoE 1, n=60)
    • One study found no analgesic benefit of saline lavage (Seo 2012; LoE 2, n=50)

PROSPECT Recommendations  

  • Local lavage with saline and then suction is recommended after removal of the gallbladder (Grade A) based on evidence of a reduction in pain scores or analgesic consumption (LoE 1). The lavage should be done with adequate suction of the remaining pneumoperitoneum (Grade A)
  • Saline lavage followed by suction was recommended in the previous review (Grade A)

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results
  • Three studies found a benefit of aspiration of pneumoperitoneum gas for reduction of pain scores compared with passive gas release (Lee 2014, LoE 1, n=75; Das 2013, LoE 2, n=200; Atak 2011, LoE 2, n=104)
    • One study showed lower pain scores at 6 h, 1 day, and 2 days (Lee 2014, LoE 1, n=75) but no significant difference in analgesic requirements
    • Another study showed lower pain scores at 1 h and 1 day (Das 2013, LoE 2, n=200). However, this was only for shoulder pain, not abdominal pain
    • The third paper showed lower pain scores at Day 1 and lower analgesic requirement (Atak 2011, LoE 2, n=104)

PROSPECT Recommendations  

  • Aspiration of pneumoperitoneum gas is recommended (Grade A) based on evidence of a reduction in pain scores (LoE 1 and 2)
  • Aspiration of pneumoperitoneum gas was not recommended (Grade D) in the previous review because of limited evidence

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results

Arguments for…

  • One study showed a 5 mm port and three 3 mm ports improved pain scores at 1 h and 1 week when compared with a 10 mm port and three 5 mm ports (Bignell 2013, LoE 1, n=79)

Arguments against…

  • One study looked at a 10 mm umbilical port together with either 3 × 5 mm ports or 3 × 3 mm ports (Alhashemi 2017, LoE 1, n=75). It showed no significant difference in pain scores between the two groups at 1 and 3 months.
  • Another study found no significant difference in pain scores or analgesic consumption with mini-LC versus conventional LC (de Carvalho 2013, LoE 2, n=42)

PROSPECT Recommendations

  • A mini-port laparoscopic technique is recommended as it reduced pain in one study (LoE 1), but the cost and availability of equipment should be taken into consideration (Grade B)
  • Mini-port was not mentioned in the previous review as no evidence was identified at that time

Laparoscopic Cholecystectomy-Specific Evidence 

Table of study details and results
  • Only one study examined the combined use of warmed and humidified CO2, showing improved pain scores at 6 h but no difference at Day 1 and no difference in analgesia requirement (Klugsberger 2014, LoE 1, n=148)

PROSPECT Recommendations

  • Warmed CO2 and humidified CO2 are not recommended (Grade D) due to limited evidence
  • Warmed CO2 was not recommended in the last review (Grade A)
  • Humidified CO2 was not recommended in the previous review (Grade D)

Laparoscopic Cholecystectomy-Specific Evidence

Table of study details and results

Arguments against…

PROSPECT Recommendations

  • Single port techniques are not recommended (Grade A) as a majority of studies found no significant benefit for analgesia (LoE 1 and 2)
  • No recommendation was made for single port techniques in the previous review as no evidence was identified