Ketamina intravenosa perioperatoria para el dolor posoperatorio agudo en adultos
Appendices
Appendix 1. CENTRAL (via CRSO)
1. MESH DESCRIPTOR Ketamine EXPLODE ALL TREES
2. ((ketamine or ketalar or calipsol or ketanest or ketaset or calypsol or kalipsol or ci‐581)):TI,AB,KY
3. #1 OR #2
4. MESH DESCRIPTOR Pain, Postoperative
5. ((postoperat* adj3 pain*)):TI,AB,KY
6. (pain* following surg*):TI,AB,KY
7. (pain* following treat*):TI,AB,KY
8. (pain* following operation*):TI,AB,KY
9. (post‐operat* pain):TI,AB,KY
10. (((post adj1 surg*) or postsurg* or post‐surg*)):TI,AB,KY
11. (((post adj1 operat*) or postoperat* or post‐operat*)):TI,AB,KY
12. pain*:TI,AB,KY
13. #10 OR #11
14. #12 AND #13
15. (((post‐operat* or postoperat* or post‐surg* or postsurg*) adj analgesi*)):TI,AB,KY
16. (analgesi* following surg*):TI,AB,KY
17. (analgesi* following operat*):TI,AB,KY
18. #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #14 OR
19. #15 OR #16 OR #17
20. #3 AND #18
Appendix 2. MEDLINE (via Ovid)
1. Ketamine/
2. (ketamine or ketalar or calipsol or ketanest or ketaset or calypsol or kalipsol or ci‐581).tw.
3. or/1‐2
4. Pain, Postoperative/
5. (postoperat* adj3 pain*).tw.
6. pain* following surg*.tw.
7. pain* following treat*.tw.
8. pain* following operation*.tw.
9. post‐operat* pain.tw.
10. ((post adj1 surg*) or postsurg* or post‐surg*).tw.
11. ((post adj1 operat*) or postoperat* or post‐operat*).tw.
12. pain*.tw.
13. (10 or 11) and 12
14. ((post‐operat* or postoperat* or post‐surg* or postsurg*) adj analgesi*).tw.
15. analgesi* following surg*.tw.
16. analgesi* following operat*.tw.
17. 4 or 5 or 6 or 7 or 8 or 9 or 13 or 14 or 15 or 16
18. 3 and 17
19. randomized controlled trial.pt.
20. controlled clinical trial.pt.
21. randomized.ab.
22. placebo.ab.
23. drug therapy.fs.
24. randomly.ab.
25. trial.ab.
26. or/19‐25
27. exp animals/ not humans.sh.
28. 26 not 27
29. 18 and 28
Appendix 3. Embase (via Ovid)
1. Ketamine/
2. (ketamine or ketalar or calipsol or ketanest or ketaset or calypsol or kalipsol or ci‐581).tw.
3. or/1‐2
4. Pain, Postoperative/
5. (postoperat* adj3 pain*).tw.
6. pain* following surg*.tw.
7. pain* following treat*.tw.
8. pain* following operation*.tw.
9. post‐operat* pain.tw.
10. ((post adj1 surg*) or postsurg* or post‐surg*).tw.
11. ((post adj1 operat*) or postoperat* or post‐operat*).tw.
12. pain*.tw.
13. (10 or 11) and 12
14. ((post‐operat* or postoperat* or post‐surg* or postsurg*) adj analgesi*).tw.
15. analgesi* following surg*.tw.
16. analgesi* following operat*.tw.
17. 4 or 5 or 6 or 7 or 8 or 9 or 13 or 14 or 15 or 16
18. 3 and 17
19. random$.tw.
20. factorial$.tw.
21. crossover$.tw.
22. cross over$.tw.
23. cross‐over$.tw.
24. placebo$.tw.
25. (doubl$ adj blind$).tw.
26. (singl$ adj blind$).tw.
27. assign$.tw.
28. allocat$.tw.
29. volunteer$.tw.
30. Crossover Procedure/
31. double‐blind procedure.tw.
32. Randomized Controlled Trial/
33. Single Blind Procedure/
34. or/19‐33
35. (animal/ or nonhuman/) not human/
36. 34 not 35
37. 18 and 36
Appendix 4. Postoperative opioid consumption in different types of surgery
24‐hour outcomes
24‐hour opioid consumption after thoracotomy
Four studies assessed opioid consumption during the first 24 hours after thoracotomy; 120 participants received ketamine and 121 participants served as controls (Argiriadou 2011; Dualé 2009; Michelet 2007; Ysasi 2010). Participants who received ketamine consumed 6 mg less opioid (95% CI ‐10.3 to ‐1.4), compared to participants who received control treatment (Analysis 5.1). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
24‐hour opioid consumption after major orthopaedic surgery
Ten studies provided data for 24‐hour opioid consumption after major orthopaedic surgery; 417 participants received ketamine and 380 participants received control treatment (Cenzig 2014; Dahi‐Taleghani 2014; Garg 2016; Hadi 2010; Jaksch 2002; Loftus 2010; Menigaux 2000; Nielsen 2017; Remérand 2009; Subramaniam 2011). Participants who had received ketamine consumed 20 mg less opioid (95% CI ‐28.6 to ‐10.8), compared to controls (Analysis 6.1). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
24‐hour opioid consumption after major abdominal surgery
Sixteen studies gave data of pain intensity at rest at 24 hours after major abdominal surgery; 544 participants received ketamine and 485 participants received control treatment (Adriaenssens 1999; Guignard 2002; Guillou 2003; Ilkjaer 1998; Kafali 2004; Kamal 2008; Katz 2004; Lehmann 2001; Parikh 2011; Roytblat 1993; Safavi 2011; Snijdelaar 2004; Stubhaug 1997; Webb 2007; Zakine 2008; Ünlügenc 2003). Ketamine treatment reduced opioid consumption by 10 mg of morphine equivalents (95% CI ‐13.8 to ‐6.8; Analysis 7.1). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
24‐hour opioid consumption after total abdominal hysterectomy
Nine studies provided data for 24‐hour opioid consumption after total abdominal hysterectomy; 260 participants received ketamine and 251 participants received control treatment (Aubrun 2008; Dahl 2000; Garcia‐Navia 2016; Gilabert Morell 2002; Hercock 1999; Karaman 2006; Murdoch 2002; Sen 2009; Yalcin 2012). Ketamine administration reduced 24‐hour opioid consumption after total abdominal hysterectomy by 5 mg of morphine equivalents (95% CI ‐10.8 to 0.4; Analysis 8.1). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
24‐hour opioid consumption after laparoscopic procedures
Four studies assessed 24‐hour opioid consumption after laparoscopic procedures; 100 participants were given ketamine and 99 participants served as controls (Ayoglu 2005; Hasanein 2011; Leal 2013; Lin 2016). Ketamine treatment reduced 24‐hour opioid consumption after laparoscopic procedures by 3 mg of morphine equivalents (95% CI ‐6.2 to 0.8; Analysis 9.1). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
48‐hour outcomes
48‐hour opioid consumption after thoracotomy
Three studies provided data of 48‐hour opioid consumption after thoracotomy; 95 participants received ketamine and 96 participants served as controls (Argiriadou 2011; Lahtinen 2004; Michelet 2007). Ketamine treatment reduced 48‐hour opioid consumption after thoracotomy by 13 mg (95% CI ‐18.3 to ‐6.7; Analysis 5.2). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
48‐hour opioid consumption after major orthopaedic surgery
Nine studies assessed 48‐hour opioid consumption after major orthopaedic surgery; 296 participants received ketamine and 261 participants received control treatment (Adam 2005; Garg 2016; Jaksch 2002; Kim 2013; Loftus 2010; Martinez 2014; Menigaux 2000; Remérand 2009; Subramaniam 2011). Participants who had received ketamine consumed 19 mg less opioid (95% CI ‐27.5 to ‐9.9), compared to participants who received control treatment (Analysis 6.2). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
48‐hour opioid consumption after major abdominal surgery
Ten studies assessed 48‐hour opioid consumption after major abdominal surgery; 381 participants received ketamine and 323 participants received control treatment (Adriaenssens 1999; Guillou 2003; Kafali 2004; Kamal 2008; Kararmaz 2003; Katz 2004; Lak 2010; Snijdelaar 2004; Webb 2007; Zakine 2008). Ketamine treatment reduced 48‐hour opioid consumption by 14 mg of morphine equivalents (95% CI ‐21.2 to ‐7.5), after major abdominal surgery (Analysis 7.2). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
48‐hour opioid consumption after total abdominal hysterectomy
Five studies provided data on 48‐hour opioid consumption after total abdominal hysterectomy; 215 participants received ketamine and 163 participants served as controls (Arikan 2016; Aubrun 2008; Dahl 2000; Gilabert Morell 2002; Yalcin 2012). Treatment with ketamine reduced 48 hour postoperative opioid consumption by 15 milligrams of morphine equivalents (95% CI ‐33.2 to 2.6; Analysis 8.2). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
48‐hour opioid consumption after laparoscopic procedures
Two studies investigated ketamine's effect on 48‐hour opioid consumption after laparoscopic procedures; 43 participants received ketamine and 42 participants received control treatment (Choi 2015; Papaziogas 2001). Ketamine treatment reduced 48‐hour opioid consumption by 5 mg (95% CI ‐12.2 to 3.3; Analysis 9.2). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
Appendix 5. Postoperative pain in different types of surgery
Pain intensity at rest at 24 hours after thoracotomy
Thirteen studies assessed pain at 24 hours at rest after thoracotomy; 388 participants received ketamine and 394 participants received control treatment (Argiriadou 2011; D'Alonzo 2011; Dualé 2009; Fiorelli 2015; Joseph 2012; Lahtinen 2004; Mendola 2012; Michelet 2007; Patel 2016; Suzuki 2006; Tena 2014; Yazigi 2012; Ysasi 2010). Visual analogue scale (VAS) scores were 4 mm lower (95% CI ‐8.8 to 1), among participants who received ketamine (Analysis 5.3). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 24 hours after thoracotomy
Five studies assessed postoperative pain intensity at 24 hours on movement after thoracotomy (Argiriadou 2011; Joseph 2012Lahtinen 2004; Tena 2014; Yazigi 2012). VAS scores were 7 mm lower (95% CI ‐20.1 to 5.5), among 154 participants who received ketamine versus 161 participants who received control treatment (Analysis 5.4). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
Pain intensity at rest at 48 hours after thoracotomy
Nine studies provided data of pain intensity at rest at 48 hours after thoracotomy (Argiriadou 2011; Chazan 2010; Fiorelli 2015; Joseph 2012; Lahtinen 2004; Mendola 2012; Michelet 2007; Suzuki 2006; Yazigi 2012). VAS scores were 7 mm lower (95% CI ‐10.4 to ‐3.4), among 265 participants who received ketamine versus 265 participants who served as controls (Analysis 5.5). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 48 hours after thoracotomy
Five studies assessed pain intensity at 48 hours during movement after thoracotomy (Argiriadou 2011; Joseph 2012; Lahtinen 2004; Suzuki 2006; Yazigi 2012). VAS scores were 11 mm lower (95% CI ‐15.3 to ‐6), among 147 participants who received ketamine versus 151 participants who received control treatment (Analysis 5.6). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
Pain intensity at rest at 24 hours after major orthopaedic surgery
Eleven studies assessed pain intensity at rest at 24 hours after major orthopaedic surgery; 449 participants received ketamine and 394 participants received control treatment (Adam 2005; Cenzig 2014; Dahi‐Taleghani 2014; Hadi 2013; Jaksch 2002; Kim 2013; Loftus 2010; Menigaux 2000; Nielsen 2017; Remérand 2009; Subramaniam 2011). VAS scores were 7 mm lower (95% CI ‐9.9 to ‐3.0) after ketamine treatment compared to those who received control treatment (Analysis 6.3). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 24 hours after major orthopaedic surgery
Four studies gave data about pain intensity at 24 hours during movement after major orthopaedic surgery; 162 participants who received ketamine had 7 mm lower VAS scores (95% CI ‐12.6 to ‐0.8), compared to 117 participants who received control treatment (Kim 2013; Menigaux 2000; Nielsen 2017; Subramaniam 2011; Analysis 6.4). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
Pain intensity at rest at 48 hours after major orthopaedic surgery
Seven studies assessed pain intensity at rest at 48 hours after major orthopaedic surgery; 246 participants received ketamine and 207 participants served as controls (Adam 2005; Jaksch 2002; Kim 2013; Loftus 2010; Menigaux 2000; Remérand 2009; Subramaniam 2011). VAS scores were 1 mm lower (95% CI ‐4.1 to 1.3), after ketamine treatment (Analysis 6.5). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 48 hours after major orthopaedic surgery
Four studies provided data of pain intensity at 48 hours during movement after major orthopaedic surgery; 95 participants experienced 7 mm lower VAS scores (95% CI ‐13.1 to ‐1.6) after ketamine treatment compared to 62 participants who served as controls (Jaksch 2002; Kim 2013; Menigaux 2000; Subramaniam 2011; Analysis 6.6). We assessed the quality of evidence for this outcome as very low. We downgraded the evidence three times because there were fewer than 400 participants in the analysis.
Pain intensity at rest at 24 hours after major abdominal surgery
Eighteen studies gave data of pain intensity at rest at 24 hours after major abdominal surgery; 637 participants received ketamine and 541 participants received control treatment (Adriaenssens 1999; Bornemann‐Cimenti 2016; Chen 2004; De Kock 2001; Guillou 2003; Joly 2005; Kafali 2004; Kakinohana 2004; Kamal 2008; Katz 2004; Lak 2010; Lehmann 2001; Parikh 2011; Safavi 2011; Snijdelaar 2004; Webb 2007; Zakine 2008; Ünlügenc 2003). VAS scores were 7 mm lower (95% CI ‐10.6 to ‐4.2), after ketamine treatment compared to controls (Analysis 7.3). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 24 hours after major abdominal surgery
Nine studies assessed pain intensity at 24 hours during movement after major abdominal surgery (Bornemann‐Cimenti 2016; De Kock 2001; Guillou 2003; Joly 2005; Kakinohana 2004; Kamal 2008; Katz 2004; Snijdelaar 2004; Webb 2007). VAS scores were 3 mm lower (95% CI ‐11.2 to 5.7), among 368 participants who received ketamine compared to 298 participants who served as controls (Analysis 7.4). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity at rest at 48 hours after major abdominal surgery
Thirteen studies provided data of pain intensity at rest at 48 hours after major abdominal surgery; 495 participants received ketamine and 396 participants received control treatment (Adriaenssens 1999; Bornemann‐Cimenti 2016; Chen 2004; De Kock 2001; Guillou 2003; Joly 2005; Kafali 2004; Kakinohana 2004; Kamal 2008; Katz 2004; Lak 2010; Webb 2007; Zakine 2008). VAS scores were 6 mm lower (95% CI ‐8.9 to ‐3.1), after ketamine treatment compared to those who received control treatment (Analysis 7.5). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 48 hours after major abdominal surgery
Nine studies assessed pain intensity at 48 hours during movement after major abdominal surgery (Bornemann‐Cimenti 2016; De Kock 2001; Guillou 2003; Joly 2005; Kakinohana 2004; Kamal 2008; Katz 2004; Snijdelaar 2004; Webb 2007). VAS scores were 3 mm lower (95% CI ‐9.2 to 3.3), after ketamine treatment among 368 participants versus 294 participants who received control treatment (Analysis 7.6). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity at rest at 24 hours after total abdominal hysterectomy
Eight studies provided data for pain intensity at rest at 24 hours after total abdominal hysterectomy; 260 participants received ketamine and 233 participants received control treatment (Arikan 2016; Aubrun 2008; Dahl 2000; Grady 2012; Hercock 1999; Lo 2008; Sen 2009; Yalcin 2012). Pain scores were 3 mm lower in VAS (95% CI ‐4.6 to ‐0.5), among those who received ketamine compared to controls (Analysis 8.3). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 24 hours after total abdominal hysterectomy
No data were available for analysis on pain intensity at 24 hours during movement after total abdominal hysterectomy.
Pain intensity at rest at 48 hours after total abdominal hysterectomy
No data were available for analysis on pain intensity at rest at 48 hours after total abdominal hysterectomy.
Pain intensity during movement at 48 hours after total abdominal hysterectomy
No data were available for analysis on pain intensity at 48 hours during movement after total abdominal hysterectomy.
Pain intensity at rest at 24 hours after laparoscopic procedures
Nine studies assessed ketamine's effect on pain intensity at rest at 24 hours after laparoscopic procedures (Ayoglu 2005; Karcioglu 2013; Kwok 2004; Leal 2013; Leal 2015; Lin 2016; Mathisen 1999; Nesek‐Adam 2012; Papaziogas 2001). Pain scores were 2 mm lower (95% CI ‐6.7 to 2.0), in VAS among 267 participants who received ketamine compared to 217 participants who served as controls (Analysis 9.3). We assessed the quality of evidence for this outcome as low, downgraded once because there were fewer than 1500 participants in the analysis, and once because it was not possible to test for small‐study effects.
Pain intensity during movement at 24 hours after laparoscopic procedures
No data were available for analysis on pain intensity at 24 hours during movement after laparoscopic procedures.
Pain intensity at rest at 48 hours after laparoscopic procedures
No data were available for analysis on pain intensity at rest at 48 hours after laparoscopic procedures.
Pain intensity during movement at 48 hours after laparoscopic procedures
No data were available for analysis on pain intensity at 48 hours during movement after laparoscopic procedures.
Appendix 6. GRADE: criteria for assigning grade of evidence
The GRADE system uses the following criteria for assigning a quality level to a body of evidence (Higgins 2011).
-
High: randomised trials; or double‐upgraded observational studies
-
Moderate: downgraded randomised trials; or upgraded observational studies
-
Low: double‐downgraded randomised trials; or observational studies
-
Very low: triple‐downgraded randomised trials; or downgraded observational studies; or case series/case reports
Factors that may decrease the quality level of a body of evidence are:
-
limitations in the design and implementation of available studies suggesting high likelihood of bias;
-
indirectness of evidence (indirect population, intervention, control, outcomes);
-
unexplained heterogeneity or inconsistency of results (including problems with subgroup analyses);
-
imprecision of results (wide confidence intervals);
-
high probability of publication bias.
Study flow diagram
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 7: Time to first request for analgesia/trigger of PCA
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 8: CNS adverse events ‐ all studies
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 9: Hyperalgesia
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 10: CNS adverse events ‐ studies with events
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 11: Postoperative nausea and vomiting ‐ all studies
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 1: Opioid consumption at 24 hours
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 2: Opioid consumption at 48 hours
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 3: Pain intensity at 24 hours
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 4: Pain intensity at 48 hours
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 5: Time to first request for analgesia/first trigger of PCA
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours
Comparison 4: CNS adverse events in studies with benzodiazepine premedication, Outcome 1: CNS adverse events
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 1: Opioid consumption at 24 hours
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 2: Opioid consumption at 48 hours
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 3: Pain intensity at rest at 24 hours
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 4: Pain intensity during movement at 24 hours
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 5: Pain intensity at rest at 48 hours
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 6: Pain intensity during movement at 48 hours
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 1: Opioid consumption at 24 hours
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 2: Opioid consumption at 48 hours
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 3: Pain intensity at rest at 24 hours
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 4: Pain intensity during movement at 24 hours
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 5: Pain intensity at rest at 48 hours
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 6: Pain intensity during movement at 48 hours
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 1: Opioid consumption at 24 hours
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 2: Opioid consumption at 48 hours
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 3: Pain intensity at rest at 24 hours
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 4: Pain intensity during movement at 24 hours
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 5: Pain intensity at rest at 48 hours
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 6: Pain intensity during movement at 48 hours
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 1: Opioid consumption at 24 hours
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 2: Opioid consumption at 48 hours
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 3: Pain intensity at rest at 24 hours
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 1: Opioid consumption at 24 hours
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 2: Opioid consumption at 48 hours
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 3: Pain intensity at rest at 24 hours
| Perioperative intravenous ketamine compared to placebo for acute postoperative pain: non‐stratified analysis | |||||
| Patient or population: adults undergoing any type of surgery Settings: immediate postoperative period Intervention: intravenous ketamine given before, during, or after surgery Comparison: intravenous placebo | |||||
| Outcomes | Details | Number of participants | Absolute values and effect of ketamine | Quality of the evidence | |
|---|---|---|---|---|---|
| Measured values with placebo | Difference with perioperative intravenous ketamine | ||||
| Opioid consumption | 24 hours | 4004 | Median 31 mg (mean 42 mg) | MD 7.6 mg lower | Moderate1 |
| 48 hours | 2449 | Median 59 mg (mean 67 mg) | MD 12.6 mg lower | Moderate1 | |
| Pain intensity | At rest 24 hours | 5004 | Median 25 mm (mean 26 mm) | MD 5 mm (VAS) lower | High2 |
| On movement 24 hours | 1806 | Median 43 mm (mean 42 mm) | MD 6 mm (VAS) lower | Moderate1 | |
| At rest 48 hours | 2962 | Median 21 mm (mean 23 mm) | MD 5 mm (VAS) lower | High2 | |
| On movement 48 hours | 1353 | Median 37 mm (mean 37 mm) | MD 6 mm (VAS) lower | Low3 | |
| Time to first request for analgesia/trigger of PCA | All data (plus analysis omitting 1 highly aberrant study reporting time of over 1000 minutes) | 1678 | Median 18 minutes (mean 39 minutes) | MD 54 minutes longer (MD 22 minutes longer omitting aberrant study (15 to 29 longer)) | Moderate4 |
| Hyperalgesia | As described, any time point | 333 | Mean 15 cm2 | MD 7 cm2 less | Very low5 |
| CNS adverse events | All events (major and minor), as described, any time point | 6538 | 52 per 1000 | 42 per 1000 RR 1.2 (0.95 to 1.4) | High6 |
| Postoperative nausea and vomiting | All studies reporting outcomes, as described, any time point | 5965 | 271 per 1000 | 230 per 1000 RR 0.88 (0.81 to 0.96 Need to treat 24 people to prevent one episode of PONV (16 to 54) | High6 |
| CI: confidence interval; CNS: central nervous system; MD: mean difference; PCA: patient controlled analgesia; PONV: postoperative nausea and vomiting; RCT: randomised controlled trial; RR: risk ratio; VAS: visual analogue scale | |||||
| GRADE Working Group grades of evidence | |||||
| 1 Downgraded once for small study effect. | |||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Opioid consumption at 24 hours Show forest plot | 65 | 4004 | Mean Difference (IV, Random, 95% CI) | ‐7.63 [‐8.88, ‐6.39] |
| 1.2 Opioid consumption at 48 hours Show forest plot | 37 | 2449 | Mean Difference (IV, Random, 95% CI) | ‐12.62 [‐15.06, ‐10.18] |
| 1.3 Pain intensity at rest at 24 hours Show forest plot | 82 | 5004 | Mean Difference (IV, Random, 95% CI) | ‐5.09 [‐6.55, ‐3.64] |
| 1.4 Pain intensity during movement at 24 hours Show forest plot | 29 | 1806 | Mean Difference (IV, Random, 95% CI) | ‐5.60 [‐10.72, ‐0.48] |
| 1.5 Pain intensity at rest at 48 hours Show forest plot | 49 | 2962 | Mean Difference (IV, Random, 95% CI) | ‐5.03 [‐6.65, ‐3.40] |
| 1.6 Pain intensity during movement at 48 hours Show forest plot | 23 | 1353 | Mean Difference (IV, Random, 95% CI) | ‐5.72 [‐10.15, ‐1.29] |
| 1.7 Time to first request for analgesia/trigger of PCA Show forest plot | 31 | 1678 | Mean Difference (IV, Random, 95% CI) | 53.89 [37.00, 70.78] |
| 1.8 CNS adverse events ‐ all studies Show forest plot | 105 | 6538 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.95, 1.43] |
| 1.9 Hyperalgesia Show forest plot | 7 | 333 | Mean Difference (IV, Random, 95% CI) | ‐7.08 [‐11.92, ‐2.23] |
| 1.10 CNS adverse events ‐ studies with events Show forest plot | 52 | 3706 | Risk Ratio (M‐H, Random, 95% CI) | 1.17 [0.95, 1.43] |
| 1.11 Postoperative nausea and vomiting ‐ all studies Show forest plot | 95 | 5965 | Risk Ratio (M‐H, Random, 95% CI) | 0.88 [0.81, 0.96] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Opioid consumption at 24 hours Show forest plot | 28 | 1639 | Mean Difference (IV, Random, 95% CI) | ‐6.26 [‐8.42, ‐4.11] |
| 2.1.1 Pre‐incisional ketamine | 19 | 1045 | Mean Difference (IV, Random, 95% CI) | ‐5.54 [‐7.95, ‐3.12] |
| 2.1.2 Postoperative ketamine | 9 | 594 | Mean Difference (IV, Random, 95% CI) | ‐8.66 [‐13.84, ‐3.49] |
| 2.2 Opioid consumption at 48 hours Show forest plot | 16 | 959 | Mean Difference (IV, Random, 95% CI) | ‐10.76 [‐14.84, ‐6.68] |
| 2.2.1 Pre‐incisional ketamine | 9 | 534 | Mean Difference (IV, Random, 95% CI) | ‐3.88 [‐7.04, ‐0.72] |
| 2.2.2 Postoperative ketamine | 7 | 425 | Mean Difference (IV, Random, 95% CI) | ‐20.81 [‐27.39, ‐14.24] |
| 2.3 Pain intensity at 24 hours Show forest plot | 29 | 1646 | Mean Difference (IV, Random, 95% CI) | ‐7.08 [‐9.56, ‐4.59] |
| 2.3.1 Pre‐incisional ketamine | 20 | 1075 | Mean Difference (IV, Random, 95% CI) | ‐6.65 [‐10.06, ‐3.24] |
| 2.3.2 Postoperative ketamine | 9 | 571 | Mean Difference (IV, Random, 95% CI) | ‐8.30 [‐12.55, ‐4.05] |
| 2.4 Pain intensity at 48 hours Show forest plot | 15 | 840 | Mean Difference (IV, Random, 95% CI) | ‐5.49 [‐7.72, ‐3.25] |
| 2.4.1 Pre‐incisional ketamine | 9 | 509 | Mean Difference (IV, Random, 95% CI) | ‐4.36 [‐7.53, ‐1.19] |
| 2.4.2 Postoperative ketamine | 6 | 331 | Mean Difference (IV, Random, 95% CI) | ‐8.02 [‐15.79, ‐0.26] |
| 2.5 Time to first request for analgesia/first trigger of PCA Show forest plot | 13 | 643 | Mean Difference (IV, Random, 95% CI) | 37.70 [20.87, 54.52] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Opioid consumption at 24 hours Show forest plot | 33 | 2176 | Mean Difference (IV, Random, 95% CI) | ‐7.31 [‐9.78, ‐4.84] |
| 3.2 Opioid consumption at 48 hours Show forest plot | 15 | 1110 | Mean Difference (IV, Random, 95% CI) | ‐14.78 [‐21.12, ‐8.44] |
| 3.3 Pain intensity at rest at 24 hours Show forest plot | 32 | 2053 | Mean Difference (IV, Random, 95% CI) | ‐8.13 [‐10.84, ‐5.42] |
| 3.4 Pain intensity during movement at 24 hours Show forest plot | 10 | 613 | Mean Difference (IV, Random, 95% CI) | ‐6.50 [‐18.97, 5.97] |
| 3.5 Pain intensity at rest at 48 hours Show forest plot | 18 | 1202 | Mean Difference (IV, Random, 95% CI) | ‐6.38 [‐9.91, ‐2.84] |
| 3.6 Pain intensity during movement at 48 hours Show forest plot | 8 | 523 | Mean Difference (IV, Random, 95% CI) | ‐4.47 [‐13.08, 4.14] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 CNS adverse events Show forest plot | 65 | 3943 | Risk Ratio (M‐H, Random, 95% CI) | 1.09 [0.86, 1.38] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Opioid consumption at 24 hours Show forest plot | 4 | 241 | Mean Difference (IV, Random, 95% CI) | ‐5.81 [‐10.28, ‐1.35] |
| 5.2 Opioid consumption at 48 hours Show forest plot | 3 | 191 | Mean Difference (IV, Random, 95% CI) | ‐12.52 [‐18.34, ‐6.71] |
| 5.3 Pain intensity at rest at 24 hours Show forest plot | 13 | 782 | Mean Difference (IV, Random, 95% CI) | ‐3.90 [‐8.80, 1.00] |
| 5.4 Pain intensity during movement at 24 hours Show forest plot | 5 | 315 | Mean Difference (IV, Random, 95% CI) | ‐7.32 [‐20.10, 5.45] |
| 5.5 Pain intensity at rest at 48 hours Show forest plot | 9 | 530 | Mean Difference (IV, Random, 95% CI) | ‐6.86 [‐10.37, ‐3.35] |
| 5.6 Pain intensity during movement at 48 hours Show forest plot | 5 | 298 | Mean Difference (IV, Random, 95% CI) | ‐10.64 [‐15.27, ‐6.00] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Opioid consumption at 24 hours Show forest plot | 10 | 797 | Mean Difference (IV, Random, 95% CI) | ‐19.68 [‐28.55, ‐10.82] |
| 6.2 Opioid consumption at 48 hours Show forest plot | 9 | 557 | Mean Difference (IV, Random, 95% CI) | ‐18.69 [‐27.47, ‐9.90] |
| 6.3 Pain intensity at rest at 24 hours Show forest plot | 11 | 843 | Mean Difference (IV, Random, 95% CI) | ‐6.45 [‐9.86, ‐3.03] |
| 6.4 Pain intensity during movement at 24 hours Show forest plot | 4 | 279 | Mean Difference (IV, Random, 95% CI) | ‐6.73 [‐12.64, ‐0.82] |
| 6.5 Pain intensity at rest at 48 hours Show forest plot | 7 | 453 | Mean Difference (IV, Random, 95% CI) | ‐1.39 [‐4.10, 1.32] |
| 6.6 Pain intensity during movement at 48 hours Show forest plot | 4 | 157 | Mean Difference (IV, Random, 95% CI) | ‐7.36 [‐13.12, ‐1.60] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Opioid consumption at 24 hours Show forest plot | 16 | 1029 | Mean Difference (IV, Random, 95% CI) | ‐10.26 [‐13.75, ‐6.76] |
| 7.2 Opioid consumption at 48 hours Show forest plot | 10 | 704 | Mean Difference (IV, Random, 95% CI) | ‐14.34 [‐21.21, ‐7.48] |
| 7.3 Pain intensity at rest at 24 hours Show forest plot | 18 | 1178 | Mean Difference (IV, Random, 95% CI) | ‐7.42 [‐10.63, ‐4.21] |
| 7.4 Pain intensity during movement at 24 hours Show forest plot | 9 | 666 | Mean Difference (IV, Random, 95% CI) | ‐2.80 [‐11.24, 5.65] |
| 7.5 Pain intensity at rest at 48 hours Show forest plot | 13 | 891 | Mean Difference (IV, Random, 95% CI) | ‐5.99 [‐8.89, ‐3.08] |
| 7.6 Pain intensity during movement at 48 hours Show forest plot | 9 | 662 | Mean Difference (IV, Random, 95% CI) | ‐2.91 [‐9.15, 3.34] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Opioid consumption at 24 hours Show forest plot | 9 | 511 | Mean Difference (IV, Random, 95% CI) | ‐5.18 [‐10.77, 0.41] |
| 8.2 Opioid consumption at 48 hours Show forest plot | 5 | 378 | Mean Difference (IV, Random, 95% CI) | ‐15.32 [‐33.20, 2.56] |
| 8.3 Pain intensity at rest at 24 hours Show forest plot | 8 | 493 | Mean Difference (IV, Random, 95% CI) | ‐2.58 [‐4.64, ‐0.52] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Opioid consumption at 24 hours Show forest plot | 4 | 199 | Mean Difference (IV, Random, 95% CI) | ‐2.67 [‐6.19, 0.84] |
| 9.2 Opioid consumption at 48 hours Show forest plot | 2 | 85 | Mean Difference (IV, Random, 95% CI) | ‐4.47 [‐12.21, 3.27] |
| 9.3 Pain intensity at rest at 24 hours Show forest plot | 9 | 484 | Mean Difference (IV, Random, 95% CI) | ‐2.32 [‐6.65, 2.02] |
