Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Fibla, 2011

Type of study:

(monocentre)

prospective randomized study

Setting and country:

University Hospital Barcelona, Spain

Funding and conflicts of interest:

None reported

Inclusion criteria:

patients with primary spontaneous pneumothorax or solitary pulmonary nodules undergoing three-ports VATS

Exclusion criteria:

secondary

pneumothorax, pregnancy, chronic preoperative analgesic treatment and opioid addiction, associated haemothorax, supra-segmental parenchymal resection, no social health insurance coverage; intraoperative

conversions of VATS into thoracotomy and revision surgery within the first postoperative 72 h

N total at baseline:

N=44

Analysis

(intervention/control)

n=40 (20/20)

n, pneumothorax/ lung nodule:

(intervention/control)

13/7 versus 12/8

Patient characteristics:

Age (yrs) ± SD:

I: 40 ± 19

C: 41 ± 19

Male sex, n:

I: 12

C: 11

Weight, kg ± SD:

I: 69 ± 10

C: 67 ± 11

Height (cm)

I: 172 ± 8

C: 173 ± 7

Groups comparable at baseline? Yes, for presented characteristics, however patient characteristics not presented separately for those with solitary nodules and pneumothorax

paravertebral block (PVB) -

at the end of the surgery, a catheter was placed in the thoracic paravertebral space under camera control; a bolus of 15 ml of

ropivacaine 0.2% was administered every 6 h, combined with i.v. metamizole (1 g)

in patients with primary spontaneous pneumothorax:

the paravertebral space catheter was inserted after resection of the lung apex, bullae or dystrophic complexes, and before pleurodesis by pleural abrasion (Marlex mesh, by scarification of the parietal pleura, except for paravertebral area and lower pleura)

-subcutaneous bolus

(50 mg) meperidine (synthetic opioid) was employed as a rescue

drug

surgical wound infiltration with bupivacaine 0.5% (5 ml for each wound) at the end of surgery and postoperative administration of i.v. paracetamol (1 g) combined with metamizole (1 g) every 6 h

-subcutaneous bolus

(50 mg) meperidine (synthetic opioid) was employed as a rescue

drug

Length of follow-up:

48 hrs after the operation;

patients were included between 2008 and 2010

Loss-to-follow-up/excluded:

four cases were excluded, three because data collection (VAS values) were incomplete and one because of accidental PVC removal

Outcome measures and effect size

Assessment of the visual analogue scale (VAS) of pain (intensity 0-10) was performed with one chest tube in place; for pneumothorax patients over 48 hrs, for patients with solitary pulmonary nodules only during 24 hrs

VAS at different time points:

PVB group:

VAS 1 h: 1.4 ± 0.8

VAS 6 h: 3.4 ± 1.2,

VAS 24 h: 2.6 ± 1.0,

VAS 48 h: 2.2 ± 0.9 (only pneumothorax cases)

mean VAS ± SD: 2.4±1.3;

control group:

VAS 1 h: 2.8 ± 1.0,

VAS 6 h: 4.9 ± 1.3,

VAS 24 h: 3.9 ± 1.4,

VAS 48 h: 3.3 ± 1.0 (only pneumothorax cases)

mean VAS: 3.8 ± 1.4.

VAS scores were significantly lower at any time in the PVB patients (p < 0.01).

requirement of rescue analgesic (meperidine)

2 patients in the control group required rescue analgesic (unclear pneumothorax or solitary nodule patients) (p<0.05)

adverse events related to the analgesia

(including respiratory depression (respiratory

rate < 8 breaths/min), cardiotoxicity, confusion, sedation, urinary retention, nausea, vomiting, and pruritus):

-no side effects related to any of the two analgesic techniques were noted;

-no intraoperative or postoperative complications in any of the patients with regard to PVC placement, local anaesthetic infusion, wound infiltration, or paracetamol and metamizole dosages;

-no complications attributable to postoperative pain

(retention of secretions, atelectasis, or pneumonia) were recorded.

-author’s conclusion:

“combining PVB inserted under direct vision + i.v. metamizole + bolus of

ropivacaine provided an excellent level of pain control’

“thoracoscopy assisted positioning of the paravertebral catheter is simple and effective, and allows direct visualization of correct delivery of local anaesthetic”

the advantage is that paravertebral blocks can be given repeatedly through the catheter in the postoperative period >6 hrs (in contrast to a single block at the beginning of the operation)

Notes:

-consecutive patients? -inclusion process unclear

-randomisation: allocated randomly by computer-generated random numbers

-blinding of nurses who measured VAS?

-blinding of patients?

Kwon, 2012

Type of study:

double-blind prospective RCT

Setting and country: Konkuk University Hospital, Konkuk University Medical Center, Konkuk

University School of Medicine, Seoul, Korea

Funding and conflicts of interest: supported by a 2012 research grant from Konkuk

University; no conflict of interest reported

Inclusion criteria:

patients >18 yrs undergoing

thoracoscopic wedge resection for pneumothorax using three-ports VATS

Exclusion criteria:

urgent or emergent case; re-do cases; preoperative coagulation

disorder (abnormal values of preoperative blood

coagulation test such as platelet count, prothrombin

time and activated partial thromboplastin time); local

or general infection; patient age <18 years; and cases

without intravenous patient-controlled analgesia (PCA) for postoperative pain control

N total at baseline:

N=53

(intervention/control)

n=26/n=27

Analysis:

n=25/n=25

Patient characteristics:

age ± SD, yrs:

I: 23 ± 7

C:26 ± 12

Sex, male:

I: 80 %

C: 84 %

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

-relaxation of the serratus anterior muscle by long thoracic nerve (LTN) block (5 ml of 0.5% lignocaine),

before induction of general anaesthesia

-postoperative patient-controlled analgesia:

alfentanil 75 µg/ml i.v.

1. 5 ml loading dose i.v. during wound dressing

2. alfentanil 15 mg (30 ml), + ondansetron

24 mg (12 ml) + normal saline 158 ml via a pump,

a continuous infusion of

1.5 ml/hour, bolus dose of 1 ml and lockout time

of ten minutes

-rescue analgesia -> bolus of alfentanil by a nurse unaware of the study

Describe control (treatment/procedure/test):

-LTN procedure without anaesthetic, same as the intervention group but with 5 ml of normal saline injection instead of lignocaine

-postoperative patient-controlled analgesia:

alfentanil 75 µg/ml i.v.

1. 5 ml loading dose i.v. during wound dressing

2. alfentanil 15 mg (30 ml), + ondansetron

24 mg (12 ml) + normal saline 158 ml via a pump,

a continuous infusion of

1.5 ml/hour, bolus dose of 1 ml and lockout time

of ten minutes

-rescue analgesia -> bolus of alfentanil by a nurse unaware of the study

Length of follow-up:

24 hours;

duration of study period/time of enrolment not described

Loss-to-follow-up:

Intervention:

N (%) n=1 (4.0%)

Reasons: malfunction in the alfentanil pump

Control:

N (%)=2 (7.4%)

Reasons: malfunction in the alfentanil pump, damage to the pump during transfer

Outcome measures and effect size

Primary outcome measure:

VAS after 10 minutes in PACU (T2)

Visual analogue scale of pain (0-100) was measured before induction of general anaesthesia (T0), on arrival to the post-anaesthetic care unit (PACU, T1), every 10 minutes after arrival in PACU for 30 minutes (T2, T3, T4), 1 hour and 24 hrs after discharge from PACU (T5, T6)

VAS at different time points:

(intervention/control)

T0: 35±7 versus 36±7 (P=0.528)

T1: 36±11 versus 48±14 (P=0.001)

T2: 36±11 versus 51±15 (P <0.001)

T3: 35±10 versus 52±15 (P <0.001) T4: 30±7 versus 45±17 (P <0.001)

T5: 26±5 versus 32±5 (P <0.001)

T6: 24±6 versus 24±8 (P=0.861)

Total bolus dose of alfentanil (patient-controlled)

-during PACU stay:

1.6±1.2 versus 3.9±2.0 ml, P <0.001

-one hour after discharge from the PACU:

0.5±0.8 versus 1.7±1.2 ml, P <0.001

-from 1-24 hrs after discharge from PACU

1.6±1.4 versus 1.1±1.3 ml, P=0.197

duration of PACU stay:

30±14 versus 54±23 min, P <0.001

author’s conclusion:

-“ LTN block reduced pain after video-assisted thoracoscopic surgery from end-of surgery to one hour after discharge from the PACU”

Notes:

-not described whether patients had primary or secondary pneumothorax

-excluded patients

without intravenous patient-controlled analgesia for postoperative pain control

-nurses evaluating pain scores were unaware of the study

Hong,

2019

Type of study:

double-blind RCT

Setting and country: Chungnam National University Hospital,

Daejeon, Korea

Funding and conflicts of interest: partially supported by Chungnam National University Hospital

Research Fund, 2018-CF-024; no conflicts of interest declared

Inclusion criteria:

Male patients 15-40 y.o., with spontaneous pneumothorax, with American Society of Anesthesiologists physical

status I or II, scheduled for wedge resection under VATS

Exclusion criteria:

refused TPVB;

coagulopathy or bleeding disorder, treatment with an antiplatelet agent, a local infection at the injection site, hypersensitive to local amide anaesthetics, hypersensitive

or allergic to dexmedetomidine; central neuropathy,

a body mass index >35 kg/m2, uncontrolled diabetes mellitus, significant cardiopulmonary disease, psychiatric disease

N total at baseline:

randomised n=66

Intervention: n=33

Control: n=33

Patient characteristics:

Median age (IQR), yrs:

I: 19 (17-22)

C: 19 (18-22)

Sex: all male patients

Median height (IQR), cm

I: 173.3 (169.5–178.2)

C: 173.1 (166.6–178.2)

Mean weight (± SD), kg

I:58.2 ± 8.0

C: 57.8 ± 8.1

Mean BM, kg/m2

I: 19.2 ± 2.2

C: 19.3 ± 2.4

Number of ports VATS, n (%)

(intervention/control)

1: 21 (63.6)/13 (39.4)

2: 2 (6.1) / 4 (12.1)

3: 10 (30.3) / 16 (48.5)

Previous history of VATS, n (%)

(intervention/control)

7 (21.2)/ 11 (33.3)

Pleural adhesion, n (%)

(intervention/control)

3 (9.1) / 9 (27.3)

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Thoracic paravertebral block with adjuvant dexmedetomidine

TPVB (0,5% ropivacaine with dexmedetomidine)

+

Patient controlled analgesia device in PACU

(0.5 µg/kg bolus dose of fentanyl, with a lockout time of 15 min and a total allowable fentanyl dose of 1000 µg)

+ rescue

(30 mg of ketorolac, followed, if necessary, by 25 mg of pethidine)

+

nefopam 20 mg (12-h interval) as part of multimodal analgesia

Describe control (treatment/procedure/test):

Thoracic paravertebral block without dexmedetomidine

TPVB (0,5% ropivacaine with normal saline)

+

Patient controlled analgesia device in PACU

(0.5 µg/kg bolus dose of fentanyl, with a lockout time of 15 min and a total allowable fentanyl dose of 1000 µg)

+ rescue

(30 mg of ketorolac, followed, if necessary, by 25 mg of pethidine)

+

nefopam 20 mg (12-h interval) as part of multimodal analgesia

Length of follow-up:

24 hrs post operation

Loss-to-follow-up:

no

Incomplete outcome data:

no

Outcome measures and effect size

Primary outcome measure:

postoperative cumulative fentanyl consumption at 24 h

I: 122.6 (IQR, 94.5–268.0) µg versus C: 348.1 (IQR,192.8–459.2) µg,

p = 0.001),

median difference

86.2 (95% confidence interval

(CI), 4.2–156.4)

analgesics request in post-anaesthesia care unit (PACU), %

I: 4 (12.1)%

C: 14 (42.4)%,

p = 0.013;

relative risk (95% CI):

0.368 (0.15–0.899)

maximum pain, numeric rating scale (NRS) at rest, 24hrs, median (IQR)

I: 4.0 (3.0–5.0)

C: 5.0 (4.0–6.0)

P=0.032

maximum pain, NRS while coughing, 24 hrs

I: 5.0 (4.0–6.0)

C: 7.0 (5.0–7.0)

P=0.003

frequency of rescue analgesics

(ketorolac)

I: 8 (24.2%)

C: 7 (21.2%), p=1.000

(pethidine)

I: 1 (3.0%)

C: 3 (9.1%), p=0.606

length of hospital stay, median days (IQR)

I: 3.0 (3.0–5.0)

C: 3.0 (3.0–5.0), p=0.455

nausea postoperatively, n (%)

I: 4 (12.1%)

C: 3 (9.1%), p=1.000

authors conclusions:

-“dexmedetomidine as an adjuvant for TPVB for postoperative pain control

after VATS had superior analgesic efficacy compared to TPVB alone”

-“dexmedetomidine reduced opioid requirement for up to 24 h after VATS”

Notes:

-range of pain scale not described

-no study group with dexmedetomidine alone (without ropivacaine) or sham block (placebo)

-only male patients included

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Yeap, 2020

Type of study:

Randomized Prospective Study

Setting and country: Academic hospital, single institution. United States

Funding and conflicts of interest: no funding received, no conflict of interest

Inclusion criteria:

- ASA classes 1 to 4
- >18 years of age,
- patient desiring regional anesthesia for adjunct postoperative pain control.

Exclusion criteria:

- contraindication to TEA or PVB,
- history of substance abuse in

the prior 6 months, - opioid tolerance,
- necessitation for intubation

after surgery,
- known allergy or contraindication to

any study medications

N total at baseline:

I 1: 40

I 2: 40

C: 40

Important prognostic factors²:

For example

age median (IQR):

I1: 64 (49-70)
I2: 62 (46-70)
C: 61 (52-70)

Sex:

I1: 40% M

I2: 47.5% M

C: 62.5% M

Intervention 1:

Preoperative: 1g paracetamol and 600mg gabapentin

Thoracic paravertebral block (PVB); ultrasound-guided catheter (placed pre-operatively) with ropivacaine 0.2% administered post-operatively at a rate of 10 ml / h by an infusion pump

Intervention 2:

Preoperative: 1g paracetamol and 600mg gabapentin

Thoracic paravertebral block (PVB); ultrasound-guided single injection 30 ml 0.5% ropivacaine, preoperative

Preoperative: 1g paracetamol and 600mg gabapentin

Thoracic Epidural Anesthesia (TEA): Infusion pump containing 0.125% bupivacaine and 0.05 mg / ml hydromorphone (starting at the end of surgery).

All groups received intravenous patient-controlled analgesia (hydromorphone, 0.2 mg, bolus dose, 10-min lock-out interval, 4 h maximum dose of 5mg) for breakthrough pain.

Length of follow-up:

72 hours, none of the patients were lost to follow-up.

Long-term follow-up

Long-term follow-up to assess for chronic postsurgical pain was conducted for 67 of the original 120 patients (single-injection PVB, n = 23; PVB catheter, n = 22; TEA, n = 22). The remaining patients were lost to follow-up.

Postoperative pain (VAS 0-10)

Postoperative median pain scores at rest were significantly different between groups at 24 hours (p = 0.02) and 48 hours (p = 0.03), with the TEA group reporting lower median scores. Pain 1h PVB-inj 5.0 (3.0-8.0) versus PVB-cath 6.0 (3.5-8.0) versus TEA 6.0 (3.0-7.5), p=0.63.

Pain 24h PVB-inj 4.0 (3.0-5.5) versus PVB-cath 4.5 (2.5-6.0) versus TEA 3.0 (1.0-5.0), p= 0.02.

Pain 48h PVB-inj 3.0 (1.0-5.0) versus PVB-cath 4.0 (2.0-6.0) versus TEA 2.0 (1.0-4.0), p= 0.03.

Pain 72h PVB-inj 3.0 (1.0-5.0) versus PVB-cath 2.0 (0-3.0) versus TEA 1.5 (0.5-4.0), p=0.22

Pain with movement differed between the groups at 24 and 48 hours, with the TEA-group the lowest scores.

Postop + rescue analgesia

Median consumption of opioids (converted to morphine milligram

equivalents (MME)) was different among groups at 24, 48, and 72 hours, with the lowest in TEA group. 24h: TEA group median of 15 MME, PVB-inj group 88 MME, PVB-cath 76 MME, p<0.001.

48h: TEA group 10 MME, PVB-inj 91 MME, PVB-cath 90. P<0.001.

72h: TEA 21 MME, PVB-inj 57, PVB-cath 35 MME, p=0.02.

Duration of hospitalization

-

Complications

no difference in major complications

Side effects

no difference between groups in nausea and sedation scores, or other major complications

Kosinski, 2016

Type of study:

RCT

Setting and country: hospital, Poland

Funding and conflicts of interest: no funding received, no conflict of interest

Inclusion criteria:

- patients qualified for VATS lobectomy due to cancer

- aged 18-85 years, of both genders,
- ASA I-III,
- understanding of the principles of VAS pain assessment

- no chronic pain.

Exclusion criteria:

- technical failures

to insert an epidural or paravertebral catheter,
- abandonment of resection (e.g., in cases of neoplastic dissemination),
- conversion of VATS to thoracotomy,
- anatomical obstacles to drug distribution found intraoperatively,
- cases in which

the VAS assessment of pain severity was infeasible
- use of other drugs affecting pain

sensations,
- artificial lung ventilation,
- discontinuation of local anaesthesia for technical reasons (e.g., catheter slipping

out or damage),
- the use of drugs or doses that were not included in the study protocol.

N total at baseline:

Intervention: 26

Control: 25

Important prognostic factors²:

For example

age median (range)

I: 60 (28–78)

C: 65 (44–73)

Sex:

I: 54% M

C: 60% M

percutaneous continuous paravertebral block (PVB)

Postoperative: regional analgaesia as well as IV ketoprofen, 100 mg every 12 h, IV paracetamol, 1000 mg every 8 h and IV morphine using PCA without a background infusion at a dose of 2−2.5 mg every 10 min and a maximum hour dose of 10 mg without an induction dose (emergency analgaesia).

continuous thoracic epidural block (TEA)

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention: 11

Failure of installation (n=1)

Lesser extent of resection (n=7)

Non-standard technique (n=1)

Postoperative artificial ventilation (n=1)

Technical failure (n=1)

Control: 16

Failure of installation (n=7)

Resection abandonment (n=1)

Lesser extent of resection (n=1)

Conversion to thoracotomy (n=3)

Postoperative artificial ventilation (n=1)

Violation of protocol (n=2)

Technical failure (n=1)

Postoperative pain (VAS range ?)

Static and dynamic pain scores at 24 postoperative hours were significantly lower in the paravertebral group (P = 0.01 and P = 0.023, respectively), as were the static pain score at 36 and 48 postoperative hours (P = 0.025 and P = 0.026).

Postop + rescue analgesia

No difference between the treatment groups was identified regarding postoperative morphine usage.

Duration of hospitalization

-

Complications

No complications were noted in either group

Side effects

side effects (urinary retention, hypotension) were more frequent in the epidural group (P < 0.05).

Okijama, 2015

Type of study:

prospective, randomized study

Setting and country: hospital, Japan

Funding and conflicts of interest: not described

Inclusion criteria:

patients (age: 18–75 years) with

ASA physical status I–III scheduled for VATS with an axillary skin incision of 6–8 cm

Exclusion criteria:

- allergy to non-steroidal anti-inflammatory drugs (NSAIDs) or LA,
- renal or hepatic failure,
- BMI > 30 kg/m2,
- infection at injection site,
- coagulative abnormality,
- inability to comprehend pain scoring.

N total at baseline:

Intervention: 36

Control: 33

Important prognostic factors²:

For example

age ± SD:

I: 61.0 ± 15.9

C: 63.0 ± 11.1

Sex:

I: M/F 20/16

C: M/F 24/9

paravertebral block (PVB);

Continuous postoperative infusion (0.1 % ropivacaine plus fentanyl at 0.4 mg/day)

Thoracic epidural block (TEB);

Continuous postoperative infusion (0.1 % ropivacaine plus fentanyl at 0.4 mg/day)

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention: 9

Extended resection(n=4)

Failed blocks(n=4)

Cancelled operation(n=1)

Control: 12

Extended resection(n=9)

Re-operations(n=1)

Failed blocks(n=1)

Postoperative renal

failure(n=1)

Postoperative pain (VRS 0-10)

There were no significant differences in VRS between group P and group E at any time

Postop + rescue analgesia

The frequencies of taking supplemental analgesics were similar in the two groups (1.0 (0.0–3.0) versus 2.0 (1.0–3.9), p= 0.26). No patient required intravenous fentanyl in either group.

Duration of hospitalization

-

Complications

Hypotension occurred significantly more frequently in TEB (n = 7/33) than in PVB (n = 1/36) (P = 0.02)

Side effects

no statistically significant differences were noted with respect to PONV and pruritus

Ding, 2018

Type of study:

RCT

Setting and country: hospital, China

Funding and conflicts of interest: This work was supported by the First Excellent Young People

Project of the Second Hospital of Harbin Medical University. No competing interests.

Inclusion criteria:

patients classified

as American Society of Anesthesiology Physical Status I/III undergoing

elective video-assisted thoracoscopic lobectomy, ages of 18 and 70 years

Exclusion criteria:

neurologic or psychiatric illnesses,
- renal or hepatic insufficiency,
- pregnancy,
- diabetes,

- allergy to local anesthetics,

- coagulation abnormalities;

- undergoing anticoagulant therapy

N total at baseline:

I1: 36

I2: 34

C: 32

Important prognostic factors²:

For example

age ± SD:

I1: 57 ± 9

I2: 53 ± 12

C: 53 ± 11

Sex:

I1: 64% M

I2: 35% M

C: 47% M

Intervention 1

PVB-R group: a preoperative single-dose 0.5% ropivacaine paravertebral block (PVB), combined with patient-controlled intravenous analgesia (PCIA) (0.01 μg/kg demand dose and 15 min lockout period with 0.03 μg/kg/h background infusion) after extubation during the 48-h postoperative period

Postoperative: flurbiprofen (50 mg every 6 h) intravenously

+ PCIA: sufentanil (0.01 μg/kg) with a 15-min lockout period and 0.03 μg/kg/h background infusion on demand

Intervention 2:

PVB-RD group: a preoperative single-dose 0.5% ropivacaine and dexmedetomidine (1μg/kg) PVB, combined with the same PCIA scheme

General anesthesia: gelijk aan controle groep

Postoperative: gelijk aan intervention 1

TEA group: intraoperative thoracic (T5/6) epidural anesthesia with 0.5% ropivacaine, and a single dose of epidural morphine (0.03 mg/kg) after extubation combined with the same PCIA scheme.

intraoperative period: patients in the TEA group received epidural infusion of 0.5% ropivacaine at 5 ml/h until skin closure, while those in the PVB-R and -RD groups did not receive additional regional anesthesia.

Postoperative: flurbiprofen (50 mg every 6 h) intravenously

+ epidural morphine (0.03 mg/kg) followed by PCIA: sufentanil (0.01 μg/kg) with a 15-min lockout period and 0.03 μg/kg/h background infusion on demand

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention 1: 2

Changed to thoracotomy (n=1)

Sensory block did not reach required level (n=1)

Intervention 2: 1

Sensory block did not reach required level (n=1)

Control: 3

Changed to thoracotomy (n=2)

Sensory block did not reach required level (n=1)

Postoperative pain: verbal rating score (VRS; scale of 0–10)

Rest: 2h: lower in the TEA than in the PVB-R and -RD groups (p<0.001 and p=0.025). No difference between the latter two groups.

6h: lower in the TEA than in the PVB-R group (p=0.003), but there was no difference between PVB-RD and -R groups.

12h: patients in the PVB-RD and TEA

groups had lower resting VRS than those in the PVB-R group (both p<0.001), but there was no difference between the PVB-RD and TEA groups.

24h: lower in the TEA group than in the other two groups (p<0.001 and p=0.004), which showed no difference between them.

36h: only the TEA group had a lower resting VRS than the PVB-R group (p=0.003).

48h: there were no among the three groups.

Coughing: 2H: no difference between the groups.

6H + 12H: PVB-RD and TEA groups had a lower cough VRS as compared to the

PVB-R group (both p<0.001), with no significant difference between the PVB-RD and

TEA groups.

24H: PVB-RD was lower as compared to the other groups (p=0.044 and p=0.002), but there was no difference between the PVB-R and TEA groups.

36H + 48h: no difference between the groups.

Postop + rescue analgesia

Patients in the PVB-RD and TEA groups received lower doses of sufentanil in the 48 h after surgery compared to PVB-R group (p=0.006 and p=0.005). Those in the PVB-RD and TEA group received extra sufentanil later after surgery than the PVB-R group (p<0.001). For both parameters, there was no significant difference between the PVB-RD and TEA groups.

Duration of hospitalization

-

Complications

-

Side effects
Patients in the PVB-RD group had a lower incidence of side effects compared to those in the TEA group.

Tseng, 2019

Type of study:

RCT

Setting and country: hospital, China

Funding and conflicts of interest: the authors have no funding and conflicts of interests to disclose

Inclusion criteria:

- 20 and 80 years

- BMI 18 - 30kg/m2, - II or III ASA classification

Exclusion criteria:

- pregnancy
- emergency,
- significant coagulopathy,
- history of chronic pain,
- conversion to open thoracotomy,
- inability to immediately extubate,
- contraindication to t-PCEA/IVPCA techniques or

drugs used in the protocol,
- thoracic spine deformities or

previous thoracic spine surgery.

N total at baseline:

Intervention: 35

Control: 35

Important prognostic factors²:

For example

age ± SD:

I: 52 ±18

C: 54 ±16

Sex:

I: 49% M

C: 53% M

Intercostal block from T1 to T6 with 1 ml 0.5% bupivacaine on each nerve: fentanyl based IVPCA including low dose ketamine (fk-IVPCA):

Post-operative: 30 mg ketorolac IV with an interval of 6 hours

Rescue analgesia: tramadol 100 mg with an interval of 8 hours.

thoracic patient-controlled epidural analgesia (t-PCEA), thoracic epidural catheter was inserted into the T4 to T8 epidural space: with 1.6 mg / ml bupivacaine combined with 1.0 μg / ml fentanyl

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention: 2

Changed to thoracotomy (n=1)

Without immediate extubation (n=1)

Control: 2

Changed to thoracotomy (n=2)

Postoperative pain (VAS 0-10)

There were no significant differences in VAS-R and VAS-M between the 2 groups at different postoperative time points
VAS-rest 48h: 0.37±0.69 versus 0.43±0.65, p=0.72. VAS-movement 48h: 2.14±1.29 versus 2.26±1.01, p=0.68

Postop + rescue analgesia

The need for rescue tramadol was similar in both groups, but the ratio of patients administered regular ketorolac was higher in the fk-IVPCA group (23 (66%) versus 31 (89%), p=0.04)

Duration of hospitalization

-

Complications

-

Side effects
The incidence of analgesic-related side effects was similar between the 2 groups

Zejun, 2018

Type of study:

RCT

Setting and country: hospital, China

Funding and conflicts of interest: supported by the Young Science

Foundation of the Affiliated Hospital of Qingdao

University. No conflict of interests.

Inclusion criteria:

- patients qualified

for VATS lobectomy as a result of cancer;

- aged 18–70 years; - of either gender;
- ASA status I–III.

Exclusion criteria:

- technical failure to insert an epidural

catheter;
- conversion of VATS to thoracotomy;
- discontinuation

of local anesthesia for technical reasons (e.g. catheter slipping out or damage);
- aged < 18 years;
- unable to provide informed consent;
- medical contraindication

for TEA according to institutional guidelines

N total at baseline:

Intervention: 49

Control: 49

Important prognostic factors²:

For example

age ± SD:

I: 55 ± 12

C: 58±8

Sex:

I: 75% M

C: 67% M

thoracic epidural analgesia (TEA), between T4 and T7

= a bolus of 5 mL of ropivacaine 0.25% preoperative + continuous perfusion of ropivacaine 0.25% at 5 mL/hour until end of surgery.

Intraoperatief analgesie onderhoud: ropivacaine solution

Postoperative: solution of ropivacaine (0.15%) and sufentanil (0.2 μg/mL) at a rate of 5–10 mL/hour with a bolus of 5 mL of the solution allowed every 40 minutes (patient-controlled epidural analgesia).

+ flurbiprofen axetil 50 mg/day

Rescue analgesia: tramadol

patient-controlled analgesia (PCA)

= general anesthesia

Intraoperatief analgesie onderhoud: sufentanil as needed

Postoperative: sufentanil was inserted at 2 μg/hour. A bolus of 2 mL was allowed every 15 minutes up to a maximal dose of 10 μg/hour.

+ flurbiprofen axetil 50 mg/day

Rescue analgesia: tramadol

Length of follow-up:

2 days

Loss-to-follow-up:

Intervention: 1

Did not receive allocated intervention (n = 1)

Control: 0

Postoperative pain (VAS 0-10)

There was no difference in scores between the groups at rest on POD 0, whereas VAS pain scores with cough on POD 0 were lower in the TEA group (P < 0.001).
Postoperative pain scores at rest and with cough on POD 1 and 2 were significantly lower in the TEA than in the PCA group.

Postop + rescue analgesia

One (3%) TEA patient and 15 (38%) PCA patients received rescue medication after surgery (P < 0.001).

Duration of hospitalization

The median postoperative hospital

stay was similar in both groups (5.0 (3.5–7.0) versus 5.0 (4.0–8.5), p= 0.94).
 

Complications

No difference in postoperative complication between groups.

Side effects
Nausea, n(%): 5 (13) versus 16 (40), p=0.006
Vomiting, n(%): 0 versus 8 (20), p=0.003

Yoshioka, 2006

Type of study:

RCT

Setting and country: hospital, Japan

Funding and conflicts of interest: not described in the article

Inclusion criteria:

- patients undergoing lobectomy or partial lung resection by VATS

Exclusion criteria:

- emergency cases

- ASA risk grade > III

- contraindication for EA

N total at baseline:

Intervention: 24

Control: 22

Important prognostic factors²:

For example

age ± SD:

I: 64 ±12

C: 62 ±10

Sex:

I: 46% M

C: 45% M

Epidural analgesia after VATS: single injection of 5 ml of 0.25% bupivacaine hydrochloride, followed by continuous infusion of 80 ml of 0.25% bupivacaine hydrochloride and 1 mg of fentanyl citrate

No epidural analgesia

Length of follow-up:

2 days

Loss-to-follow-up:

None reported

Postoperative pain (VAS 0-100, Verbal Pain Score-rest 0-3, VPS-movement 0-2)

The mean VAS in the EA group was significantly lower than in the NEA group at 0 POD (p=0.045), but there was no significant difference at 1 and 2 POD.
Difference in VPS-R was significant at 0 POD (p=0.003) and 1 POD (p=0.046), in favour of EA group.

The difference in VPS-M was significant from 0 to 2 POD (p<0.0001), in favour of EA group.

Postop + rescue analgesia

Rectal diclofenac sodium and intramuscular pentazocine were needed more frequently in the NEA group than in the EA group (p<0.05). Total doses of diclofenac sodium and pentazocine per patient were also higher in the NEA group than in the EA group (p=0.004 and p<0.0001).

Duration of hospitalization

-

Complications

One patient in NEA group had air leakage for more than 7 days after VATS, none of the other patients in both groups suffered from any postoperative complications.

Side effects
7 (29%) patiënt in de EA group suffered nausea or vomiting, which was higher than in the NEA group (1 patiënt, 5%, p<0.05).

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Fibla, 2011

allocated randomly by computer-generated random numbers

unclear

Allocation concealment not described in the paper

unlikely

Blinding of patients not described in the paper, due to the nature of intervention (block using a catheter versus medication only) blinding of patients not possible

unlikely

Blinding of surgeon impossible (placing a catheter versus no catheter and pain medication i.v.)

unclear

Blinding of outcome (pain score) for assessor (nurse) not reported

likely

did not report data per indication for VATS (primary spontaneous pneumothorax versus solitary pulmonary nodules); outcome assessment for the primary outcome measure was performed at different time intervals depending on indication (48 hrs for pneumothorax and 24 hrs for pulmonary nodules)

likely

excluded patients because of incomplete data collection (VAS scores), unclear in which group (except 1 with accidental PV catheter removal)

likely

patients excluded after randomisation, unclear from which group

Kwon, 2012

randomly assigned to either group by opening sealed envelopes that revealed the

group to which they would be assigned

unclear

not described how precisely the random sequence had been generated (before sealing envelopes)

unclear

LTN block with an anaesthetic or normal saline was administered before general anaesthesia, the effectiveness of the block was measured by the inability of arm abduction beyond 90 degrees in a sitting position

unclear

anaesthetists performed LTN block before the start of general anaesthesia, unclear whether the allocation to intervention or control arm was revealed at the moment of block

unlikely

nurses recording pain scores were unaware of the study

unlikely

unlikely

the number of lost to follow-up was very small

likely

not all randomized patients were included in the analysis due to technical issues with the pump providing patient-controlled anaesthesia

Hong, 2019

after induction of general anaesthesia, the study subjects were randomized 1:1 to the

intervention group or

control group using a computer-generated

random number table with a block size of four.

unlikely

(random number

table was saved in Redcap software, which was used for randomization and data management, this was available to researches preparing study drugs and these researches were not involved in monitoring of patients and analysing outcomes)

unlikely

(all patients underwent the block procedure)

unlikely

(study drugs were prepared in space other than the operation room, researchers performing blocks were blind to the allocation and study drugs)

unclear

(the paper does not describe who assessed the outcomes, eg. recording of pain score)

unlikely

unlikely

unlikely

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Yeap, 2020

Randomization was performed using Research Randomizer

Unlikely

Unclear

Unclear

Unlikely
Investigators were blinded

Unlikely

Unlikely

Unclear

Kosinski, 2016

Method not described

Unclear

Unlikely

Unclear

Unlikely

Unlikely

Unlikely

Unclear

Okijama, 2015

Randomization was performed using sealed envelope technique

Unclear

Unclear

Unclear

Unclear

Unlikely

Unlikely

Unclear

Ding, 2018

Method not described

Unclear

Unclear

Unclear

Unlikely

Unlikely

Unlikely

Unclear

Tseng, 2019

Randomization was performed using computer-generated codes that were kept in

sequentially numbered opaque envelopes

Unlikely

Unclear

Unclear

Unclear

Unlikely

Unlikely

Unclear

Zejun, 2018

Randomization was performed using a computer-generated random number table with sealed envelopes

Unlikely

Likely

No blinding

Likely

No blinding

Likely

No blinding

Unlikely

Unlikely

Unclear

Yoshioka, 2006

Randomization was performed using envelopes

Unlikely

Unclear

Unclear

Unclear

Unlikely

Unlikely

Unclear