Supplementary Materials

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Supplementary Materials

Table of Contents

Appendix A: Search Strategies

Appendix B: List of Important Excluded Studies and Protocols Appendix C: Detailed Characteristics of Included Studies Appendix D: Detailed Risk of Bias Assessments

Appendix E: Subgroup Forest Plots for Each Outcome as Appropriate Appendix F: Funnel Plots for Each Outcome

Appendix A: Search Strategies

Database: Ovid MEDLINE(R) ALL <1946 to February 09, 2022>

Search Strategy:

--- 1 Craniotomy/ (13947)

2 Trephining/ (1629)

3 Decompressive Craniectomy/ (1673) 4 Scalp/ (14353)

5 (craniectomy* or craniotomy*).mp. (27018) 6 burrhole.mp. (79)

7 (brain adj3 (surg* or operat*)).mp. (9301) 8 (post?craniotom* or post craniotom*).mp. (331) 9 (post?craniectom* or post craniectom*).mp. (59) 10 exp Brain Neoplasms/su [Surgery] (33919) 11 or/1-10 (79314)

12 exp Analgesics/ (563852) 13 exp Anesthetics, Local/ (108347) 14 local anesthetic.mp. (12991) 15 lidocaine.mp. (33919) 16 bupivacaine.mp. (17555) 17 mepivacaine.mp. (2718) 18 ropivacaine.mp. (5593)

19 scalp block.mp. or Nerve Block/ (20489) 20 or/12-18 (669861)

21 10 and 20 (341)

22 randomized controlled trial.pt. (558338) 23 controlled clinical trial.pt. (94693) 24 randomized.ab. (550240)

25 placebo.ab. (225542) 26 drug therapy.fs. (2441562) 27 randomly.ab. (375787) 28 trial.ab. (587114) 29 groups.ab. (2309526) 30 or/22-29 (5257777)

31 exp animals/ not humans.sh. (4956807) 32 30 not 31 (4575011)

33 21 and 32 (188)

***************************

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <January 2022>

Search Strategy:

--- 1 Craniotomy/ (427)

2 Trephining/ (15)

(2)

3 Decompressive craniectomy/ (34) 4 Scalp/ (348)

5 (craniectomy* or craniotomy*).mp. (1766) 6 burrhole.mp. (6)

7 (brain adj2 (surg* or operat*)).mp. (1329) 8 (post?craniotom* or post craniotom*).mp. (99) 9 (post?craniectom* or post craniectom*).mp. (5) 10 exp Brain Neoplasms/su [Surgery] (192) 11 or/1-10 (3282)

12 exp Analgesics/ (54174) 13 exp Anesthetics, Local/ (16351) 14 local anesthetic.mp. (6945) 15 lidocaine.mp. (13947) 16 bupivacaine.mp. (14250) 17 mepivacaine.mp. (1021) 18 ropivacaine.mp. (6989)

19 scalp block.mp. or Nerve Block/ (4041) 20 or/12-18 (84583)

21 10 and 20 (55)

***************************

Database: Embase <1974 to 2022 February 10>

Search Strategy:

--- 1 craniotomy/ (35222)

2 brain surgery/ (12635) 3 skull surgery/ (6507) 4 craniectomy/ (6306)

5 decompressive craniectomy/ (4787) 6 (craniotom* or craniectom*).mp. (50688) 7 burr hole.mp. (2591)

8 trephining.mp. (148)

9 (brain adj3 (surg* or operat*)).mp. (23014) 10 (post?craniotom* or post craniotom*).mp. (498) 11 (post?craniectom* or post craniectom*).mp. (80) 12 scalp/su [Surgery] (379)

13 or/1-12 (78650)

14 exp analgesic agent/ (1019382) 15 exp local anesthetic agent/ (251898) 16 nerve block/ (34516)

17 scalp block.mp. (179)

18 adrenalin hydrogen tartrate plus lidocaine/ or ceftriaxone plus lidocaine/ or bupivacaine plus lidocaine/ or dexamethasone sodium phosphate plus lidocaine/ or lidocaine plus phenylephrine plus tropicamide/ or adrenalin plus lidocaine/ or lidocaine plus polymyxin B/ or lidocaine plus phenylephrine/ or lidocaine ethobromide/ or lidocaine plus prilocaine/ or lidocaine/ or hyaluronic acid plus lidocaine/ or lidocaine plus tetracaine/ (79341) 19 epinephrine plus mepivacaine/ or mepivacaine/ or mepivacaine plus neocobefrin/ (6104)

20 ropivacaine/ (13548) 21 bupivacaine/ (40178) 22 lidocaine.mp. (83060) 23 mepivacaine.mp. (6343) 24 ropivacaine.mp. (13921) 25 bupivicaine.mp. (499) 26 or/14-25 (1203694) 27 13 and 26 (4644)

28 Randomized controlled trial/ or Controlled clinical study/ or random$.ti,ab. or randomization/ or intermethod

comparison/ or placebo.ti,ab. or (compare or compared or comparison).ti. or ((evaluated or evaluate or evaluating or

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assessed or assess) and (compare or compared or comparing or comparison)).ab. or (open adj label).ti,ab. or ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. or double blind procedure/ or parallel

group$1.ti,ab. or (crossover or cross over).ti,ab. or ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. or (assigned or allocated).ti,ab. or (controlled adj7 (study or design or trial)).ti,ab. or (volunteer or volunteers).ti,ab. or human experiment/ or trial.ti.

(5661757)

29 ((random$ adj sampl$ adj7 (cross section$ or questionnaire$1 or survey$ or database$1)).ti,ab. not (comparative study/ or controlled study/ or randomi?ed controlled.ti,ab. or randomly assigned.ti,ab.)) or (Cross- sectional study/ not (randomized controlled trial/ or controlled clinical study/ or controlled study/ or randomi?ed controlled.ti,ab. or control group$1.ti,ab.)) or (((case adj control$) and random$) not randomi?ed controlled).ti,ab. or (Systematic review not (trial or study)).ti. or (nonrandom$ not random$).ti,ab. or Random field$.ti,ab. or (random cluster adj3 sampl$).ti,ab. or ((review.ab. and review.pt.) not trial.ti.) or (we searched.ab. and (review.ti. or review.pt.)) or update review.ab. or (databases adj4 searched).ab. or ((rat or rats or mouse or mice or swine or porcine or murine or sheep or lambs or pigs or piglets or rabbit or rabbits or cat or cats or dog or dogs or cattle or bovine or monkey or monkeys or trout or marmoset$1).ti. and animal experiment/) or (Animal experiment/ not (human experiment/ or human/)) (3889834)

30 27 and 28 (947) 31 30 not 29 (837)

***************************

Database: ClinicalTrials.gov <March 2022>

Term: Scalp Block (22 results)

***************************

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Appendix B: List of Important Excluded Studies and Protocols

No important studies were identified which were not included in analysis. Review of ClinicalTrials.gov identified 22 study protocols. Of these, 13 trials have been completed. Six have unknown status. Two are actively recruiting. One was withdrawn.

Identifier Status Patient

Number Design Outcome

NCT02916264 Unknown, last update

2016. 30 Scalp Block vs Placebo Analysis of intraoperative anesthetic and hemodynamic factors NCT02558569 Completed, 2016. 128 Scalp Block vs Placebo Analysis of intraoperative fentanyl requirement and emergence time NCT02852382 Completed, 2017.

Included in this review. 45 Scalp Block vs Incisional infiltration vs Placebo. Posterior fossa only.

Analysis of intraoperative hemodynamic factors, postoperative pain one to 24 hours (VAS), and morphine consumption in one to 24 hours

NCT03776617 Unknown, last update Feb 2019 recruiting with estimated Dec 2019 completion.

120 Scalp block (two arms) versus Placebo vs No Procedure

Analysis of intraoperative opioid consumption, hemodynamic factors, emergence time, and pain (NRS) at three months.

NCT04955236 Completed, 2021. 40 Scalp block vs

Systemic Analgesia.

Posterior fossa only.

Analysis of initial systolic blood pressure, intraoperative hemodynamic and medication consumption, emergence time, and agitation score one hour after surgery.

NCT03667352 Completed, 2018. 60 Scalp block +

transverse abdominis plane block vs Placebo. Abdominal cranioplasty only.

Analysis of postoperative opioid requirement, pain (VAS), intraoperative hemodynamics.

NCT04133467 Completed, 2019.

Observational trial. 26 Scalp Block versus historical controls.

Crainoplasty only.

Analysis of postoperative pain, resumption of oral nutrition.

NCT03177252 Withdrawn, 2017. 200 Scalp block vs Placebo Investigator did not proceed with trial

NCT04240236 Completed, 2020. 40 Scalp Block vs No

Procedure Analysis of postoperative nausea and vomiting, intraoperative hemodynamic factors, intraoperative fentanyl consumption, emergence time.

NCT04344132 Unknown, last update

2020. Not yet recruiting. Unknown Scalp Block Preop vs

Postop Postoperative pain (VAS), intraoperative hemodynamics and opioid consumption, time to first postoperative rescue analgesia.

Included in review. 150 Scalp Block (2 arms) versus Incisional Infiltration

Postoperative pain (NAS), pain at three months, postoperative sedation scale, rescue analgesic consumption, intraoperative hemodynamics, cognitive function, postoperative nausea and vomiting,

Included in review. Scalp block (2 arms)

vs Placebo Intraoperative mean arterial pressure

NCT03411330 Completed, 2018. 64 Scalp block with

hyaluronidase versus Scalp Block

Postoperative pain, intraoperative hemodynamics, interleukin six level, intraoperative opioid dose, time to analgesic request, hemodynamic effects.

NCT02880566 Unknown, last updated

2016. Not yet recruiting. 50 Scalp Block vs Placebo Intraoperative hemodynamic factors, intraoperative remifentanil consumption, postoperative pain, postoperative morphine consumption.

NCT02057367 Completed, 2016. 100 Scalp Block vs Placebo Intraoperative opioid consumption, intraoperative hemodynamic factors, time to extubation.

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NCT04648358 Recruiting, 2020. 98 Scalp Block vs Scalp Block with Dexamethasone

Postoperative opioid requirement, postoperative pain (NRS), intraoperative sufentanil consumption, postoperative glasgow coma scale, emergence delirium, length of stay, patient satisfaction score, intraoperative hemodynamics.

NCT03073889 Unknown. Last updated

2017. Recruiting. 45 Scalp Block vs

Incisional Infiltration vs No Procedure

Interleukin six level, intraoperative hemodynamic factors, postoperative pain (VAS)

NCT04034836 Recruiting, 2020. 132 Scalp Block vs Scalp

Block with IV Parecoxib vs Placebo

Time to rescue analgesia, postoperative pain (NRS), glasgow coma scale, intraoperative sufentanil, postoperative nausea and vomiting, intraoperative hemodynamics, time in postoperative care unit, length of stay, adverse events, patient satisfaction scores.

NCT02428283 Completed, 2017. 44 Scalp Block vs No

Procedure Change in Watcha behavior scale for emergence agitation.

NCT02939833 Unknown. Last updated

2016. Not yet recruiting. 160 Scalp Block vs Placebo Serum TNF-alpha, interleukin six, interleukin one beta, postoperative pain (VAS + NRS), pain control medication, incidence of intracranial infection, hospitalization days, expenditure for hospitalization.

Included in review. 89 Scalp Block vs Placebo Posoperative pain (VAS), postoperative hydromorphone

consumption, postoperative nausea and vomiting, time to discharge eligibility from PACU/ICU, time to discharge eligibility from hospital, long term pain, Karnofsky Performance Scale.

NCT03648034 Completed, 2020. 144 Scalp Block vs Placebo Karnofsky Performance Scale, TNF-alpha level, interleukin six level, interleukin one beta level, Iowa satisfaction with anesthesia scale, white blood cell count, C-reactive protein, postoperative pain (VAS), pain relief medications, length of stay, expenditure for hospitalization, complications

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Appendix C: Detailed Characteristics of Included Studies

Stu dy ID

Nu mbe r of Pati ents Cou

ntry Inclusion

criteria Exclusion criteria Interv

ention Control Pain Scale Used

Timi ng of Scalp Block

Opiat e Used

Interv ention Age (Mean years +/- SD)

Contr ol Age (Mean years +/- SD)

Interve ntion Gender (% Male)

Control Gender (% Male)

Inter venti on Surg ery Type

Cont rol Surg ery

Type Adverse Events

Akcil 2017³

2 47 Turke y

ASA I-III, 18- 70yo, scheduled infratentorial craniotomy

Relevant allergy, chronic HTN, CAD, arrhythmia, coagulopathy, cerebrovascular disease, raised ICP, trigeminal neuralgia, previous craniotomy

Bupivac aine 0.5%

A: Remifenta nil 50 ug IV. B:

Incisional bupivacai ne 0.5%

Visual Analog ue Scale

Before craniot

omy Codeine 40.6 +/- 15.89

A: 38.8 +/- 18.7.

B: 38.46

+/- 10.8 46.7 A: 26.7.

B: 26.7.

Infrate ntorial : 15

A: Infrate ntorial : 15.

B: Infrate ntorial

: 15. None reported.

Ayoub 2006³

3 50 Cana

da

ASA I-III, 18- 70yo, scheduled supratentorial craniotomy

Unable to use VAS, relevant allergy, planned incision extending beyond the field of the block, narcotic use >2wks, alcohol abuse, active psychiatric disorders

Lidocai ne 2% + Bupivac aine 0.5%

Placebo scalp block + IV morphine (0.1mg/kg )

Numeri c Analog ue Scale

After craniot omy Tramad

ol 51 +/- 14 47 +/-

12 56 60

Suprat entoria l: 25

Suprat entoria

l: 25 No difference in hemodynamics

Bala 2006³

4 40 India

ASA I-II, 18- 50yo, scheduled supratentorial

craniotomy GCS<15, relevant allergy

Bupivac aine 0.5% + epineph rine 1:400,0 00

Placebo scalp block + epinephrin e 1:400,000

After craniot omy Morphi

ne 36.8 +/- 8.5 40.1 +/-

9.3 50 75

No arrhythmia or hypotension was noted during block or postoperatively

Can 2017³

5 90 Turke y

ASA I-II, 18- 85yo, scheduled craniotomy

Relevant allergy. Uncontrolled HTN, arrhythmia, DM, coagulopathy, or CAD.

A: Bupivac aine 0.5%.

B: Levobu pivocai ne 0.5%

Placebo scalp block

Before craniot omy Morphi

ne 49.03 +/- 15.81

A: 49.2 +/- 9.95.

B: 47.6

+/- 17.31 36.7 A: 50. B:

36.7

Not Report ed

No intraoperative arrhythmia/asystol e, no tinnitus, paresthesias, deafness.

Carell a 2021³

6 60 Belgi um

ASA I-III, scheduled supratentorial craniotomy, estimated OR length 90- 360min

Contraindications to scalp block (known allergy, local infection), age >75 or <18, obesity (BMI>35), emergency craniotomies, chronic pain (persistent/recurrent pain lasting

>3 months), fibromyalgia, drug addiction, chronic alcohol abuse, treatment with corticosteroids from >6months, uncontrolled hypertension, severe kidney or liver disease, mental disorders, serious neurological diseases, cardiomyopathies or sustained cardiac arrhythmias.

Major blood loss - patients excluded from analyses

Levobu pivacain e 0.33%

Placebo scalp block

Before craniot

omy 57, range 22-78

57, range

30-78. 43 43

Suprat entoria

l: 30 None reported.

Dudko 2014³

7 75 Lithu ania

ASA I-III, scheduled supratentorial

craniotomy None listed

Bupivac aine 0.25% + lidocain e 1% + epineph rine 1:200,0 00

A: Paracetam ol 1g IV + ketoprofe n 2 mg/kg IV. B:

Incisional bupivacai ne 0.25%

+ lidocaine 1% with

After craniot omy

Ketorol ac 30 mg IV, paraceta mol 1 g IV, and pethidin e 50 mg IM

Not specified .

Not specified

. Not

specified. Not specified.

Not Report ed

Not Report

ed None reported.

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epinephrin e 1:200.000

El-Daha b 2009³

8 80 Egypt ASA I-III, 65+yo

Relevant allergy, GCS<14, 'huge' tumor with midline shift, surgeries lasting>6h, planned incision extending beyond the field of the block, uncontrolled HTN

Bupivac aine + epineph rine

Saline wound infiltration + epinephrin e 1:400,000 + fentanyl 2mcg/kg prior to pinning

Before craniot omy

Fentany l IV by PCA 69.3 +/-

2.3 71.1 +/-

1.9 52.8 64.1

Fits' - Intervention 6/36 (15%), Control 4/30 (10%). No change in ICP between groups.

Gazoni 2008³

9 30

Unite d States

18+yo, scheduled supratentorial craniotomy for tumor

“Pregnancy, the presence of a preexisting intracranial defect (for example, from a previous craniotomy), allergy to remifentanil or ropivacaine, or a history of malignant

hyperthermia.”

Ropivac aine 0.5% No

procedure Visual Analog ue Scale

Before craniot omy

Morphi ne IV via PCA

Not specified .

Not specified

. Not

specified. Not specified.

Suprat entoria

Girar d 2010¹

4 30 Cana

da

ASA I-III, 18- 70yo, scheduled infratentorial or occipital craniotomy

Unable to use VAS, relevant allergy, planned incision extending beyond the field of the block, chronic opioid medications (>2 weeks), history of alcohol abuse, active psychiatric disorders

Bupivac aine 0.5% + Lidocai ne 2%

with Placebo 10ml IV

Placebo scalp block + morphine 0.1mg/kg in 10ml IV after dural closure

After craniot

omy 55 +/- 13 45 +/-

11 46.7 40

Infrate ntorial / Occipi tal: 15

Infrate ntorial / Occipi

tal: 15 None reported.

Herna ndez Palaz on 2007⁴

0 30 Spain

ASA I-III, 18- 69yo, scheduled supratentorial craniotomy for

tumor Unable to use VAS, relevant allergy

Placebo scalp block + epinephrin e 1:200,000

After craniot omy

Meperi dine 100mg

IM 52 +/- 13 43 +/-

16 60 53.3

Suprat entoria

Hussi en 2020⁴

1 30 Egypt

ASA I-II, 21- 60yo, scheduled supratentorial craniotomy for tumor, BMI<35

GCS<14, huge tumour midline shift. Incision extending beyond the areas covered by regional scalp block. Infiltration of scalp preoperatively along future incision or postoperatively along the wound edges only. Previous craniotomy and chronic use of analgesics or drug dependence.

Uncontrolled hypertension.

Surgeries lasting more than 6 hours or patient needing postoperative ventilatory support or any complications during the procedure such as massive ICH

Bupivac aine 0.25% + lidocain e 1% + epineph rine 1:200,0

00 No

Before craniot

omy 42.9 +/- 11.7 42.07

+/- 11.1 66.7 73.3

Suprat entoria

Hwang 2015⁴

2 52 South Korea

ASA I-II, 19- 75yo, scheduled frontoparietal craniotomy for aneurysm clipping

Unable to use VAS, relevant allergy, GCS<14, ruptured aneurysm and SAH, allergic reaction to local anesthetics, previous craniotomy incision, chronic use of opioids for >2 weeks, active psychiatric disorders

+ epineph rine 1:200,0 00

Placebo scalp block

After craniot omy

58 (median) , 54-65 (IQR)

56 (median) , 53-64

(IQR) 30 26

dizziness 4%

sleeping tendency 26% delirium 17%

Mostafa 2020⁴

3 40 Egypt

ASA I-II, 18- 80yo, 70-80 kg, scheduled supratentorial craniotomy for tumor, requiring head pinning

Relevant allergy, pregnancy, DM, chemotherapy or radiation therapy during the previous 7 days, GCS<15. Withdrawal criteria included procedures requiring only one burr hole or duration of surgery longer than 8 hours.

Bupivac aine 0.5% No

Before craniot

omy 50.45 +/- 11.722 49.9 +/-

13.31 50 55

Suprat entoria

(8)

Nguyen 2001⁴

4 30 Cana

da

ASA I-III, 18- 70yo, scheduled supratentorial craniotomy

Unable to use VAS, relevant allergy, planned incision extending beyond the field of the block, narcotic use >2wks

Ropivac aine 0.75%

Placebo scalp block

After craniot

omy 48 +/- 12 48 +/- 9 53.3 33.3

Suprat entoria

Raksa kietis ak 2018⁴

5 130 Thail and

ASA I-III, 18- 75yo, GCS 15, 'good communicatio n', scheduled supratentorial craniotomy for single <4 cm tumor.

Relevant allergy, unstable hemodynamics including uncontrolled high blood pressure or need for inotropic / vasopressor drugs,

coagulopathy, liver disease, BMI>=30, suspected brain herniation.

Placebo scalp block

Before craniot omy Oxycod

one 47.5 +/- 11.8 48.9 +/-

12.2 26.6 25

No infections, hematoma, nerve injury, nerve palsy, or other

complications from scalp block. No hypotension, malignant arrhythmia, or any major adverse cardiac events in either group.

Two patients in each group developed postoperative neurological deficits, all of which improved prior to discharge.

Rigamonti 2020⁴

6 89 Cana

da

ASA I-III, 18+yo, scheduled supratentorial craniotomy

Conditions contraindicating the use of the anesthesia protocol, potential difficulties to discern postoperative pain specifically related to surgery

Placebo scalp block

After craniot

omy 54 +/- 15 55 +/-

15 36 53

Suprat entoria

Skutu liene 2021⁴

7 141 Lithu ania

ASA I-III, 19- 75yo, scheduled supratentorial craniotomy for tumor

Relevant allergy, GCS<15, long-term analgesic or corticosteroid therapy, cardiac arrhythmias, impaired liver function

Bupivac aine 0.25% + lidocain e 1% + epineph rine 1:200,0 00

A: Paracetam ol 1g IV Ketoprofe n 2mg/kg IV. B:

Incisional Bupivacai ne 0.25%

+ lidocaine 1% + epinephrin e 1:200,000

After craniot omy

Hydrom orphone , Dezocin

e 56.1 A: 56.4

B: 59.1. 31.9 A: 27.7.

B: 34

A: Suprat entoria l: 47.

B: Supate ntorial

: 47. None reported.

Tuchi nda 2010⁴

8 60 Thail and

ASA I-II, 16- 65yo, scheduled supratentorial craniotomy

Unable to use VAS, relevant allergy, HTN, opioid

dependence, coagulopathy, scalp infection, previous craniotomy

A: Bupivac aine 0.5% + epineph rine 1:200,0 00. B:

Bupivac aine 0.25% + epineph rine 1:200,0 00.

Placebo scalp block NS + epinephrin e 1:200,000

Before craniot omy

A: 37 +/- 12. B: 35 +/- 12 31 +/-

10. A: 50. B:

42 70

B: Suprat entoria l: 19.

One patient in intervention group B experienced postoperative hematoma and was excluded from the study.

No postoperative scalp infections or scalp hematomas observed in any patients.

Valla pu 2018⁴

9 150 India

ASA I-II, 18- 70yo, scheduled craniotomy

Relevant allergy, planned incision extending beyond the field of the block, chronic narcotic or analgesic use, planned for postoperative mechanical ventilation, postoperative GCS<15, poor

Bupivac aine 0.25% + dexmed etomidi ne (1 mcg/kg)

A: Incisional bupivacai ne 0.25%.

B: Incisional bupivacai ne 0.25%

After Craniot omy

Nalbup hin, Fentany l 37.5 +/-

13.4

A: 42.2 +/- 14.3.

B: 39 +/-

14.3. 52 A: 54. B:

72

Suprat entoria l: 43, Infrate ntorial : 7

A: Suprat entoria l: 44, Infrate ntorial : 6. B:

Suprat

Intervention pain at 1-month 7/50 (14%), pain at 3 months 2/50 (4%).

Control A pain at 1-month 15/50 (30%), pain at 3 months 5/50

(9)

cognitive function, fever >39, or

mechanical ventilation postop + dexmedet omedine (1 mcg/kg).

entoria l: 42, Infrate ntorial : 8

(10%). Control B pain at 1-month 20/50 (40%), pain at 3 months 6/50 (12%)

Wang 2022⁵

0 151 China

ASA I-II,18- 70yo, single intracranial lesion, scheduled craniotomy

“Preoperative change in consciousness, disease history that could affect postoperative functional recovery (e.g., paralysis, autoimmune disease, acute or decompensated heart failure or acute coronary syndrome, or severe liver or renal malfunction)”, had participated in another study within the last 3 months

Ropivac aine 0.5% No

procedure Numeri c Analog ue Scale Unspec

ified Morphi ne 52.9 +/-

10.5 50.6 +/-

9.7 39.5 42.7

Mortality: 0 Infection: 1 (1.3%) Seizure: 0 Hemorrhage: 0 High ICP: 0 CSF leak: 0 Delirium: 1 (1.3%) Resp depression: 0 Cardiovascular complication: 0 Resp complication:

1 (1.3%) Digestive complication: 0 Urinary complication: 0 VTE/DVT: 0 30-day reoperation: 0 30-day readmit: 0

Yang 2019⁵

1 57 China

ASA I-II, 18- 65yo, scheduled craniotomy for anterior aneurysm clipping

Unable to use VAS, relevant allergy, difficult surgical anatomy or multiple or giant aneurysms, previous craniotomy incision, history of drug dependence or alcohol abuse, GCS<14

Ropivac aine 0.75%

A: No procedure.

B: Incisional Ropivacai ne 0.75%.

Before craniot omy Pethidin

e 55.94 +/- 5.14

A: 54.41 +/- 6.62.

B: 55.19

+/- 5.94 33.3 A: 23.5.

B: 25

B: Suprat entoria l: 16

No respiratory depression, cutaneous pruritus, subcutaneous hematomas, scalp infection, or local anesthetic toxicity.

Intervention dizziness = 1/18, Fever = 1/18.

Control A Dizziness = 1/17, Fever = 1/17.

Control B Dizziness = 0/16, Fever = 2/16

Yang 2020⁵

2 88 China

ASA I-II, 18- 60yo, scheduled craniotomy, BMI 18-30

Unable to use VAS, relevant allergy, GCS<15, “history of opioid dependence,

coagulopathy, scalp infection, pregnancy and previous craniotomy. Withdrawal criteria included aphasia,

unconsciousness, postoperative mechanical ventilation and duration of surgery longer than 6 hours”

A: Ropivac aine 0.5%.

B: Ropivac aine 0.33%.

C: Ropivac aine 0.25%.

Placebo scalp block

Before craniot omy

Any opiod given after emerge nce

A: 46.41 +/- 11.26. B:

52.9 +/- 10.5. C:

50.6 +/- 9.7 44.14

+/-13.28 A: 50. B:

60. C:

52.38 31.88

Not Report ed

No postoperative scalp infections, scalp hematoma, or

‘local or general complications’ in any patients.

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Appendix D: Detailed Risk of Bias Assessments

D1. Risk of Bias of Pain Outcomes (RoB 2 Tool). Note that risk of bias was not different between any time points.

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D2. Risk of Bias of Opioid Consumption Outcomes (RoB 2 Tool). Note that risk of bias was not different between any time points.

D3. Risk of Bias of Postoperative Nausea and Vomiting (RoB 2 Tool).

(12)

D4. Risk of Bias of Duration of Surgery (RoB 2 Tool).

D5. Risk of Bias of Hospital Length of Stay (RoB 2 Tool).

(13)

Appendix E: Subgroup Forest Plots For Each Outcome As Appropriate E1. Visual Analogue Score Subgroup and Sensitivity Analyses

Visual Analogue Scale Equivalent Pain at 2 Hours

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(15)

(16)

(17)

(18)

(19)

Visual Analogue Scale Equivalent Pain at 6-8 Hours

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(21)

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Visual Analogue Scale Equivalent Pain at 12 Hours

(24)

(25)

(26)

(27)

(28)

(29)

(30)

(31)

(32)

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E2. Opioid Consumption Subgroup and Sensitivity Analyses

Opioid Consumption At 24 Hours

(34)

(35)

Opioid Consumption at 48 Hours

(36)

E3. Postoperative Nausea and Vomiting Subgroup and Sensitivity Analyses

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(38)

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E4. Length of Surgery Subgroup and Sensitivity Analyses

(40)

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Appendix F: Funnel Plots For Each Outcome

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