Anaesthesia 2022, 77, 311–325 doi:10.1111/anae.

15609

Guidelines

PROSPECT guidelines for video-assisted thoracoscopic

surgery: a systematic review and procedure-specific
postoperative pain management recommendations
S. Feray,1 J. Lubach,2 G. P. Joshi,3 F. Bonnet4 and M. Van de Velde5 on behalf of the
PROSPECT Working Group *of the European Society of Regional Anaesthesia and Pain
Therapy

1 Assistant Professor, 4 Professor, Department of Anaesthesia, Intensive Care and Peri-operative Medicine, H^
opital
Tenon, Paris, France
2 Resident, Department of Anaesthesiology, 5 Professor, Department of Cardiovascular Sciences, KU Leuven and
University Hospital Leuven, Leuven, Belgium
3 Professor, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center,
Dallas, TX, USA

Summary
Video-assisted thoracoscopic surgery has become increasingly popular due to faster recovery times and
reduced postoperative pain compared with thoracotomy. However, analgesic regimens for video-assisted
thoracoscopic surgery vary significantly. The goal of this systematic review was to evaluate the available
literature and develop recommendations for optimal pain management after video-assisted thoracoscopic
surgery. A systematic review was undertaken using procedure-specific postoperative pain management
(PROSPECT) methodology. Randomised controlled trials published in the English language, between January
2010 and January 2021 assessing the effect of analgesic, anaesthetic or surgical interventions were identified.
We retrieved 1070 studies of which 69 randomised controlled trials and two reviews met inclusion criteria. We
recommend the administration of basic analgesia including paracetamol and non-steroidal anti-inflammatory
drugs or cyclo-oxygenase-2-specific inhibitors pre-operatively or intra-operatively and continued postoperatively.
Intra-operative intravenous dexmedetomidine infusion may be used, specifically when basic analgesia and
regional analgesic techniques could not be given. In addition, a paravertebral block or erector spinae plane block
is recommended as a first-choice option. A serratus anterior plane block could also be administered as a second-
choice option. Opioids should be reserved as rescue analgesics in the postoperative period.

.................................................................................................................................................................
Correspondence to: M. Van de Velde
Email: [email protected]
Accepted: 28 September 2021
Keywords: analgesia; evidence-based medicine; postoperative pain; systematic review; video-assisted thoracoscopic
surgery
This article is accompanied by an editorial by Singh and Ramachandran, Anaesthesia, 2022; 77: 252–6.
*See Appendix 1.
Twitter: @MarcVandeVelde6

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Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit
commercial exploitation.

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Anaesthesia 2022, 77, 311–325 Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery

Recommendations concerning pain after thoracotomy recommended using a

1 Regional analgesic techniques such as paravertebral regional analgesic technique such as a continuous
block and erector spinae plane block are paravertebral or thoracic epidural block [5]. As VATS is less
recommended. Serratus anterior plane block can be painful, Bendixen et al. suggested using less invasive
used as a second choice. regional analgesic techniques or systemic analgesia [2].
2 Systemic analgesia should include paracetamol and non- However, patients can still experience severe pain after
steroidal anti-inflammatory drugs or cyclo-oxygenase-2- VATS [1]. In this setting, pain management is just as essential
specific inhibitors administered pre-operatively or intra- as it is for open surgery as it might reduce postoperative
operatively and continued postoperatively. complications [2]. Systemic analgesia is evolving with
3 Intra-operative administration of intravenous multimodal analgesia using intravenous (i.v.) medications
dexmedetomidine is recommended when basic like lidocaine, a2-adrenergic agonists or N-methyl-D-
analgesics cannot be given. aspartate (NMDA) antagonists. Several regional analgesic
4 Opioids should be used as rescue analgesics techniques have also been developed to manage thoracic
postoperatively. postoperative pain such as the paravertebral block, the
5 Thoracic epidural analgesia is not recommended for erector spinae plane (ESP) block and the serratus anterior
postoperative analgesia. plane block. There is consequently a need to determine the
most appropriate analgesic technique(s) or protocol(s) to
Why was this guideline developed? control pain after VATS.
Video-assisted thoracoscopic surgery (VATS), although less The PROSPECT Working Group is a collaborative
painful than thoracotomy, is associated with significant group of surgeons and anaesthetists working together to
acute and chronic postoperative pain, negatively affecting formulate procedure-specific recommendations for pain
recovery [1, 2]. This guideline aims to provide clinicians with management after common but potentially painful surgical
an evidence-based approach to pain management after procedures. The recommendations are based on a
pulmonary resection under VATS, and to improve procedure-specific systematic review of randomised
postoperative pain relief. controlled trials followed by Delphi rounds to formulate and
agree recommendations. The methodology considers
What other guidelines are available on clinical practice, efficacy and adverse effects of analgesic
this topic? techniques [6, 7].
In 2018, Piccioni et al. published an enhanced recovery after In this study, we aimed to summarise the literature on
surgery programme for thoracic surgery [3]. Batchelor et al. pain control after VATS over the past 10 y and retrieved the
also published guidelines for enhanced recovery after evidence regarding pre-, intra- and postoperative pain
surgery for all types of thoracic surgical procedures [4]. management strategies. The primary outcome included
postoperative pain scores and opioid requirements. Other
How does this guideline differ from recovery outcomes, including postoperative nausea and
other guidelines? vomiting and other adverse effects, were also assessed
The procedure-specific postoperative pain management when reported and the limitations of the data were
(PROSPECT) approach to developing guidelines is unique reviewed. The ultimate objective was to develop
such that the available evidence is critically assessed for recommendations for pain management after VATS.
current clinical relevance. This approach reports true clinical
effectiveness in the setting of a specific surgical procedure Methods
by balancing the invasiveness of the analgesic interventions This review was performed in accordance with the PROSPECT
and the degree of pain after surgery, as well as balancing methodology [6–8]. Specific to this study, the Embase;
efficacy and adverse effects. Compared with previous MEDLINE; PubMed; Cochrane Central Register of Controlled
guidelines, PROSPECT guidelines focus on pain Trials; Cochrane Database of Abstracts of Reviews of Effects;
management in the specific setting of VATS. and Cochrane Database of Systematic Reviews were
searched for randomised controlled trials published between
Introduction 01 January 2010 and 01 January 2021. We focused on this
Video-assisted thoracoscopic surgery is a minimally invasive time period because VATS was uncommonly performed for
procedure allowing the reduction of surgical stress and lung resection in the preceding years, with thoracotomy
postoperative pain. Previous PROSPECT guidelines being the standard of care at that time.

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Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery Anaesthesia 2022, 77, 311–325

Search terms used were related to pain and concealment (A, adequate; B, unclear; C, inadequate; D, not
interventions for VATS. These comprised ‘video-assisted used), numerical (1–5) quality scoring system used by Jadad
thoracoscopic surgery’ and/or ‘thoracoscopic’ and/or et al. to assess randomisation, blinding and flow of patients;
‘video-assisted wedge’ and/or ‘video-assisted lobectomy’ follow-up of more or less than 80% of the included patients;
and/or ‘pain’ and/or ‘analgesia’ and/or ‘anaesthesia’ and/or and whether the study met the requirements of the
‘anesthetic’ and/or ‘visual analogue’ and/or ‘vrs’ and/or CONSORT 2010 statement. The suggested recommendations
‘mcgill’ and/or ‘epidural’ and/or ‘neuraxial’ and/or ‘spinal’ were sent to the PROSPECT Working Group for
and/or ‘paravertebral block’ and/or ‘erector spinae’ and/or review and comments through a modified Delphi
‘serratus block’ and/or ‘intercostal block’ and/or approach as previously described [9]. Once consensus
‘suprascapular block’ and/or ‘intrathecal’ and/or ‘caudal’ was achieved, the lead authors drafted the final
and/or ‘intrapleural’ and/or ‘narcotic’ and/or ‘continuous document, which was ultimately approved by the
intercostal nerve block’ and/or ‘combined epidural-general’ Working Group.
and/or ‘combined regional-general’ and/or ‘NMDA’ and/or
‘peripheral block’ and/or ‘infiltration’ or ‘instillation’ or Results
‘NSAID’ or ‘COX-2’ or ‘paracetamol’ or ‘acetaminophen’ or A total of 69 randomised controlled trials were included in
‘gabapentin’ or ‘pregabalin’ or ‘clonidine’ or ‘opioid’ or the final qualitative analysis (Fig. 1). These studies are listed
‘ketamine’ or ‘corticosteroid’ or ‘dexamethasone’ or in the online Supporting Information (Table S1) with their
‘magnesium’ or ‘lidocaine’ or ‘patient-controlled analgesia’ respective methodological quality scores. Online
or ‘PCA’ or ‘PEC block’ or ‘transcutaneous electrical nerve Supporting Information (Tables S2 and S3) describe the
stimulation’ and/or ‘TENS’. characteristics of included studies.
We included randomised controlled trials and
systematic reviews published in English assessing pain Paracetamol and NSAIDs
management for patients undergoing VATS for lung Jahangiri et al. [10] compared paracetamol with ketorolac
resection. We excluded studies with patients who administered after VATS and continued as a postoperative
underwent a thoracotomy and studies in which more than continuous infusion. They did not receive any additional
75% of the included patients underwent surgery for baseline analgesia but had i.v. morphine as a rescue. No
pneumothorax, as the peri-operative pain profiles varied significant difference was documented between the
from VATS for lung resection. These studies were removed ketorolac and paracetamol groups in pain scores; morphine
from analysis because pleural abrasion or resection consumption; and patient satisfaction. The volume of blood
prevents the use of some regional anaesthetic techniques in thoracic drains was significantly higher in the ketorolac
such as paravertebral block. Pain control after group (309 ml vs. 273 ml; p = 0.001) but the difference was
pneumothorax surgery is an issue that is somewhat different not clinically relevant. There was no difference in other side-
from pain control after lung resection, and the aim of effects.
PROSPECT review being to provide clinicians appropriate Dastan et al. [11] compared three groups of patients
recommendations applying specifically for dedicated receiving either morphine 20 mg, paracetamol 4 g or
surgical procedures. ketorolac 120 mg at the end of surgery and continued for
Quality assessment, data extraction and data analysis the first day, with i.v. morphine 0.05–0.1 mg.kg-1 used as
adhered to the PROSPECT methodology [7]. The studies rescue analgesia, with no multimodal analgesia provided.
were required to measure pain intensity using a visual They found no difference in pain scores between the three
analogue scale (VAS) or a numeral rating scale (NRS). We groups. Mean (SD) VAS scores on coughing were
defined a change of more than 10 on a scale of 0–100 as significantly higher in the morphine group throughout the
clinically relevant. We used the PROSPECT methodology study period (3.5 (2.5) in the morphine group; 1.4 (1.4) in
previously described for the assessment of the study the ketorolac group; and 2.7 (2.6) in the paracetamol
protocols and results [9]. A p value of <0.05 was considered group). The number of patients who needed rescue
to be statistically significant, and if two or more studies mediation was higher in the paracetamol group; however,
achieved a significant difference, we considered there to be the mean dose of morphine given as rescue was
enough data to recommend the treatment or the technique. comparable in the three groups. There was a clinically
Recommendations were made according to the unimportant difference in the volume of blood loss
PROSPECT methodology [9]. Criteria for the assessment of between the groups (ketorolac 291 ml; paracetamol
the quality of eligible studies included allocation 250 ml; and morphine 169 ml).

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Anaesthesia 2022, 77, 311–325 Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery

Figure 1 Flow diagram of studies identified, screened and included in this systematic review.

Intravenous a2-adrenergic agonists there were no differences in the incidence of hypotension or

-1
Lee et al. compared i.v. dexmedetomidine 1 lg.kg vs. bradycardia between the two groups.
saline control 20 min before the end of surgery [12]. No Jannu et al. [13] also compared two groups of patients
basic analgesia (e.g. paracetamol, NSAIDs) was reported, receiving either i.v. dexmedetomidine or saline. They
but all patients received a loading dose of fentanyl 1 lg.kg-1 started with a 1 lg.kg-1-loading dose of dexmedetomidine
followed by a continuous infusion of 0.4 lg.kg-1.h-1. before induction followed by a 0.5 mg.kg-1 infusion until
Baseline quality of recovery (QoR)-40 global and 20 min before the end of surgery. All patients received
dimensional scores were comparable in the two groups. i.v. paracetamol every 8 h for the first 72 h after surgery.
Pain NRS scores at rest and coughing and opioid Tramadol was used as rescue and there was no additional
consumption were significantly lower in the baseline analgesia. They documented a significant
dexmedetomidine group compared with the control group reduction in pain scores and rescue medication (72% of
(rescue fentanyl needed in 58% of patients in the patients in the intervention group vs. 92% of patients in the
dexmedetomidine group vs. 82% of patients in the control control group) in the dexmedetomidine group during the
group) during the first 24 h. More patients were agitated on first 24 h. Patients in the intervention group also had a
emergence from anaesthesia in the control group. Forced better FEV1 and shorter hospital stay. Hypotension and
expiratory volume for 1 s (FEV1) was significantly greater in bradycardia were not reported in this study.
the dexmedetomidine group compared with the control Kweon et al. [14] compared a postoperative i.v. infusion
group on the first and second days after surgery. Nausea of a low dose (0.15 µg.kg-1.d-1) of dexmedetomidine vs.
and vomiting were more frequent in the control group, but saline. The use of basic analgesia (paracetamol, NSAIDs)

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Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery Anaesthesia 2022, 77, 311–325

was not reported. Patients in both groups had i.v. sufentanil all patients. They found no difference in pain scores or
patient-controlled analgesia (PCA). Sufentanil requirement patient satisfaction.
and pain scores at rest and on movement were lower in the There was only one study comparing different opioids
dexmedetomidine group during the first 24 h. for postoperative pain control. However, morphine was
Postoperative nausea and vomiting were lower in the commonly used as a rescue to treat postoperative pain
dexmedetomidine group. There was no difference between using PCA and opioid (commonly morphine) consumption
the two groups in the occurrence of bradycardia at 1 h, 4 h, was used as an outcome in most studies. There was no study
8 h and 24 h postoperatively. Mean arterial blood pressure assessing anaesthesia with different opioids (remifentanil;
was lower in the dexmedetomidine group at 8 h sufentanil; fentanyl) or without opioids (opioid-free
postoperatively but the difference was not clinically anaesthesia).
relevant.
Miao et al. [15] compared a loading dose of Steroids
dexmedetomidine intra-operatively followed by an i.v. Bjerregaard et al. [18] compared high-dose
dexmedetomidine PCA (0.1 µg. kg-1.h-1) vs. a loading dose methylprednisolone (125 mg) before surgery with placebo.
of saline intra-operatively followed by an i.v. sufentanil PCA. Baseline analgesia included paracetamol, ibuprofen and
All patients had NSAIDs and an intercostal nerves block gabapentin, supplemented by paravertebral block and an
performed by the surgeon at the end of the surgical intercostal nerves block, with morphine or a bolus of
procedure. There was no significant difference between the bupivacaine in the intercostal nerves block given as rescue.
two groups in pain scores or rescue analgesia. The On the day of surgery, pain scores at rest and during
incidence of nausea and vomiting was significantly lower in mobilisation were significantly reduced in the
the dexmedetomidine group. A significant reduction in methylprednisolone group (1.7 vs. 2.5) but not during arm
mean arterial blood pressures, heart rate and sufentanil abduction or coughing. Pain scores on the first and second
consumption was observed within 48 h after surgery in the days after surgery, and opioid consumption were
dexmedetomidine group compared with the sufentanil comparable. Side-effects were comparable in the two
group. groups, except that patients in the methylprednisolone
Wang et al. [16] compared a loading dose of group needed more insulin for high blood glucose levels.
dexmedetomidine administered at the end of surgery plus Indeed, corticosteroid boluses lead to an increase in blood
dexmedetomidine PCA vs. a loading dose of saline sugar levels. We do not know if this transient hyperglycaemia
followed by saline PCA. The use of basic analgesia has any relevant clinical consequences. There were no
(paracetamol and NSAIDs) was not reported, and included studies assessing dexamethasone in this setting.
oxycodone was provided to all patients. No additional
baseline analgesia was used. Median VAS pain scores (2 in N-methyl-D-aspartate (NMDA) antagonists
the dexmedetomidine group vs. 4 in the oxycodone group) We did not retrieve any studies assessing the use of
and median oxycodone consumption (13 mg in the ketamine in VATS. One study aiming to assess both
dexmedetomidine group vs. 16 mg in the saline group) dexmedetomidine and ketamine has been registered in
were significantly lower in the dexmedetomidine group cinicaltrials.gov (NCT03596424). Sohn et al. [19] studied the
until 24 h after surgery, and nausea and vomiting were also administration of an i.v. bolus of magnesium sulphate of
lower. There was no difference between the two groups in 50 mg.kg-1 for 10 min, followed by a continuous infusion of
the occurrence of bradycardia at different time-points 50 mg.kg-1.h-1 during surgery after tracheal intubation,
assessed. followed by a continuous infusion until the end of the
We did not include any studies that assessed the use of surgery vs. a control group with saline. A fentanyl PCA
clonidine in VATS. associated with a basal i.v. infusion was started at the end of
surgery. Basic analgesia (NSAIDs) was used at the discretion
Systemic opioid analgesia of the physicians incharge of the patients. The mean opioid
Bai et al. [17] compared different opioids and modalities of demand was significantly lower in the magnesium sulphate
administration. They compared three groups: i.v. morphine group compared with the control group (35.1 mg vs.
PCA without basal infusion; i.v. hydromorphone PCA with a 44.7 mg at 24 h). Pain scores and rescue analgesics were
basal infusion; or i.v. hydromorphone PCA without basal comparable in both groups. Postoperative FEV1 and forced
infusion. Basic analgesia (paracetamol and NSAIDs) was not vital capacity were higher in the magnesium group when
reported. Surgeons performed intercostal nerves block in compared with the control group.

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Gabapentinoids intra-operatively by surgeons. Giang et al. [26] compared

Kim et al. [20] documented that a single administration of this technique with i.v. morphine PCA and noted
pregabalin before surgery decreased postoperative pain significantly lower pain scores only during the first 4
scores up to 24 h and the need for additional rescue postoperative hours. Opioid consumption was higher in the
analgesics without an increase in the incidence of side- PCA group. Baseline analgesia was not reported. There was
effects. Patients did not receive any additional baseline no difference in side-effects. Lee et al. [27] did a comparable
analgesia in this study. study, with an i.v. fentanyl PCA. All patients received
Konstantatos et al. [21] reported that the tramadol and paracetamol as basic analgesia. They also
administration of pregabalin before and for 5 days after documented lower opioid consumption in the
surgery was associated with did not reduce pain scores paravertebral group with no difference in pain scores
or postoperative opioid consumption. All patients between groups. There was a higher incidence of
received paracetamol and port sites were infiltrated with postoperative nausea and vomiting and discontinuation of
a ropivacaine solution. i.v. fentanyl PCA in the PCA group. Wu et al. [28] compared
Homma et al. [22] administered pregabalin for paravertebral catheter to systemic analgesia with i.v.
3 months from the second postoperative day. All patients sufentanil PCA. All patients received systemic NSAIDs.
received NSAIDs and had thoracic epidural analgesia for Mean VAS was not significantly different between groups
2 days after surgery. The number of patients who but morphine consumption was significantly higher in the
experienced postoperative neuropathic pain was sufentanil PCA group. There was significantly more
significantly lower in the pregabalin group compared with postoperative nausea and vomiting and more rescue
the control group (19.6% vs. 41.3%, respectively). However, analgesia in the sufentanil PCA group.
the delay between surgery and the occurrence of Four studies focused on the paravertebral single-shot
postoperative neuropathic pain was comparable between technique. Zhang et al. [29] documented a lower VAS
groups. score on coughing and lower opioid consumption in the
paravertebral single-shot group (performed by the
Intravenous lidocaine surgeon under direct vision) compared with local wound
Slovack et al. [23] compared the administration of an i.v. infiltration. All patients received NSAIDs and i.v. morphine
lidocaine bolus after the induction of anaesthesia followed PCA as a rescue. A recent study from Chu et al. [30] found
by continuous infusion until the end of surgery vs. placebo. lower pain scores and lower opioid consumption in the
Basic analgesia was not reported. They found no significant single-shot paravertebral block group (performed by an
difference in pain scores and opioid consumption. anaesthetist) compared with the control group with no
block. All patients received NSAIDs and i.v. sufentanil PCA
Transcutaneous electrical nerve stimulation (TENS) as a rescue. Another study by Chu et al. [31] compared
Regarding the use of TENS, we found two studies with three different groups. The first group received a pre-and
different results. Engen et al. [24] compared TENS plus postoperative paravertebral injection performed by the
opioid analgesia vs. opioid analgesia alone. Basic analgesia anaesthetist using ropivacaine 2 mg.ml-1, the second
was not reported. No difference in analgesia or opioid group only received a postoperative injection and the third
consumption was observed. group had a sham block with saline. The basic analgesia
Chen et al. [25] compared transcutaneous electrical protocol was not reported. No significant difference in
acupuncture points stimulation vs. placebo TENS using very pain scores was documented between the three groups.
low amperage. Basic analgesia was not reported and no There was a significant decrease in opioid use in the pre-
additional baseline was used. They found a reduction in and postoperative group compared with the other groups.
mean VAS pain scores up to 48 h postoperatively (3.2 vs. Kang et al. [32] examined the effect of ultrasound-guided
5.8, 2.9 vs. 6.0, 1.7 vs. 2.9 at 6 h, 24 h and 48 h in TENS and paravertebral blocks on rehabilitation using the decline
control groups, respectively), with reduced consumption of rate of the six-minute walking test (6MWT) on
rescue morphine. postoperative day 1 as the primary outcome. Basic
analgesia use was not reported. There was a lower decline
Regional analgesia rate of 6MWT on postoperative days 1 and 2 in the
Paravertebral block paravertebral group compared with the control group.
We included three studies assessing continuous Postoperative analgesic consumption was also lower in the
paravertebral blocks with catheter placement performed paravertebral group.

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Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery Anaesthesia 2022, 77, 311–325

Hutchins et al. [33] compared continuous paravertebral paracetamol. There was no significant difference between
block with ropivacaine 2 mg.ml-1 infused at 10–14 ml.h-1 the two groups in terms of pain score and opioid
through a catheter placed by the anaesthetist vs. single-shot consumption.
-1
intercostal nerves block with ropivacaine 2.5–5.0 mg.ml Kaya et al. [42] looked at multiple injections (five
performed by the surgeon. Basic and baseline analgesia injections from T4 to T8) vs. a single injection at T6. Multiple
were not reported. They found lower pain scores in the injections were more painful and took longer to be
paravertebral catheter group but no difference in opioid performed but both the analgesic effect and opioid
use. Kadomatsu et al. [34] compared a continuous consumption were similar.
paravertebral vs. intercostal nerves block, with a catheter Regarding the combination of opioids with local
placed by a surgeon in both instances. Basic analgesia was anaesthetic for paravertebral block, we only found one study.
provided with NSAIDs. They found no significant difference Bauer et al. [43] compared continuous paravertebral block
between the two groups. with ropivacaine plus sufentanil vs. ropivacaine alone. There
Several studies assessed the addition of was no significant difference between the two groups for
dexmedetomidine to paravertebral blocks. Xu et al. [35] pain scores and opioid consumption.
looked at multilevel paravertebral blocks with ropivacaine Taketa et al. [44] compared an intercostal approach vs.
plus dexmedetomidine vs. plain ropivacaine. Basic a paralaminar approach to paravertebral block. This study
analgesia was provided with NSAIDs. They observed lower suggested that the paralaminar approach provided
pain scores in the dexmedetomidine group but similar superior analgesia. In the paralaminar group the number of
opioid consumption. Hong et al. [36] used a similarly postoperative fentanyl rescue doses was lower than that
designed protocol but with nefopam as baseline analgesia intercostal group at 3 h, 6 h, 12 h and 24 h postoperatively.
and NSAIDs as a rescue analgesia and found lower pain scores
and reduced opioid consumption in the dexmedetomidine Erector spinae plane block
plus ropivacaine group. Abd-Elshafy et al. [37] compared We found two studies that compared single-shot erector
paravertebral block with bupivacaine 5 mg.ml-1 plus spinae plane (ESP) block performed with 20 ml bupivacaine
dexmedetomidine vs. plain bupivacaine. They observed only 5 mg.ml-1 vs. a control group with no block. Patients were
a significant decrease in pain and only within the first 2 h. administered NSAIDs for basic analgesia. Ciftci et al. [45]
Opioid consumption was not reported. They found a concluded that patients having ESP blocks had lower active
reduction of chronic pain at 3 months but not at 6 months in and passive pain scores and lower opioid consumption during
the dexmedetomidine group as a secondary outcome. the first 24 h, as well as a lower incidence of postoperative
Ding et al. [38] compared three groups: thoracic nausea and vomiting. Liu et al. [46] also compared single-shot
epidural plus a single dose of epidural morphine vs. single- ESP vs. no block. Results were similar, with lower pain scores
shot paravertebral vs. single-shot paravertebral with and lower opioid consumption. A secondary outcome was a
dexmedetomidine. They found that patients in the faster postoperative out-of-bed activity. No basic analgesia
dexmedetomidine paravertebral group and those in the (paracetamol and NSAIDs) was reported.
thoracic epidural group had significantly lower pain scores. Two other studies compared ESP block with
Different modalities of administration of local ropivacaine vs. placebo block with saline. Yao et al. [47]
anaesthetics by a paravertebral catheter have been studied. found that ESP block with ropivacaine reduced pain scores
Taketa et al. [39] looked at programmed intermittent bolus at rest and during coughing for the first 8 h after surgery.
vs. continuous infusion for postoperative analgesia. They Non-steroidal anti-inflammatory drugs were used as basic
failed to demonstrate a significant difference in analgesia, analgesia. Postoperative sufentanil utilisation was lower in
opioid consumption and postoperative nausea and the first 24 h; QoR-40 scores were higher on the first and
vomiting. There were, however, a larger number of second postoperative days; patients were discharged
dermatomes anaesthetised in the programmed intermittent earlier; and patient satisfaction was higher in the ESP block
bolus group. Chen et al. [40] did a similar study with a smaller group than the sham group. Shim et al. [48] performed a
number of patients. They found lower pain scores at rest and similar study, but no basic analgesia was stated. They
with coughing in the programmed intermittent bolus group reported lower pain scores in the ESP block group in the first
and also lower consumption of local anaesthetic. 6 h, but not after this time-point. Rescue opioid use,
Kamalanathan et al. [41] looked specifically at the however, was lower in the placebo group. As with Yao et al.,
timing of the block, either after incision or at the end of the length of stay was also significantly shorter in the ESP block
procedure. Basic analgesia was supplied by NSAIDs and group.

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Two studies compared ESP with paravertebral blocks. serratus anterior plane block group, and patients used less
Zhao et al. [49] compared single-shot ESP block vs. single- tramadol as rescue medication in this group. Non-steroidal
shot paravertebral block in patients receiving infusions of anti-inflammatory drugs were given in both groups as
NSAIDs for basic analgesia. They found no significant routine analgesia. Park et al. [55] found lower pain scores
difference in pain scores, quality of recovery or opioid and opioid in the first 24 h in patients who received deep
consumption during the first 48 h. Taketa et al. [50] serratus anterior plane block compared with those who did
compared continuous ESP blocks with paravertebral not. Routine analgesia was used, with paracetamol and
blocks with no basic analgesia. They also found no NSAIDs. Viti et al. [56] reported better pain control with
difference in pain scores or opioid consumption during deep serratus anterior plane blocks using baseline
the first 48 h. Chen et al. [51] compared three groups: ESP analgesia with tramadol and NSAIDs. Opioid consumption
block vs. paravertebral block vs. intercostal nerves block. was not reported in this study. Semyonov et al. [57]
There were no additional baseline and basic analgesia was documented lower pain scores in the first 8 h and
not reported. They observed that opioid consumption and significantly lower opioid consumption among patients who
pain scores at rest and while coughing were significantly received serratus anterior plane block (either a deep or a
lower in the paravertebral block group compared with the superficial injection at the operator’s discretion).
ESP block and intercostal nerves block groups up to 8 h Postoperative nausea and vomiting were lower in the
postoperatively. There was no significant difference in pain serratus anterior plane block group. Paracetamol and
scores between ESP block and intercostal nerves block NSAIDs were given to both groups as basic analgesia.
groups during the first 48 h. Turhan et al. [52] also Kim et al. [58] used an intervention group with
compared ESP block, paravertebral block and intercostal superficial serratus anterior plane block with ropivacaine vs.
nerves block. Patients all received basic analgesia with saline. They found that pain scores at rest were lower in the
paracetamol and NSAIDs. Pain scores were lower in the serratus anterior plane block group, with lower opioid
paravertebral block group compared with the intercostal consumption and less postoperative nausea and vomiting.
nerves block group and lower in the intercostal nerves Basic analgesia was applied with paracetamol, codeine and
block group compared with the ESP block group. NSAIDs.
Morphine consumption was lower in the intercostal nerves Chen et al. [59] allocated patients to one of two
block and the paravertebral block groups compared with groups: superficial serratus anterior plane block or local
the ESP block group. There was no difference in morphine anaesthetic infiltration before the surgical incision. They
consumption between the paravertebral block and reported a difference in pain scores favouring the serratus
intercostal nerves block groups. There was no difference anterior plane block group at 2 h and 8 h after surgery, but
between the three groups in mobilisation times. not later. During the first 8 h, opioid consumption in the
Gao et al. [53] studied three groups with different serratus anterior plane block group was lower. No basic
adjuvants combined with ropivacaine in ultrasound-guided analgesia was reported in any group. Shang et al. [60] also
ESP block where NSAIDs were used as basic analgesia. The compared superficial serratus anterior plane block vs. local
first group received plain ropivacaine, the second group anaesthetic infiltration of the surgical incision. Basic
had ropivacaine plus dexamethasone and the third group analgesia included NSAIDs. The estimated median time to
had ropivacaine plus dexmedetomidine. They reported that the first VAS ≥4 was significantly longer in the serratus
the dexmedetomidine group had reduced pain scores, anterior plane block group. Kim et al. [61] compared deep
lower need for rescue analgesia and shorter hospital stay serratus anterior plane block vs. intercostal nerves block
compared with the other two groups. but found no significant difference in both opioid
consumption and pain scores. Paracetamol was used as
Serratus anterior plane block basic analgesia. Lee et al. [62] also compared ultrasound-
Serratus anterior plane blocks can be performed by guided superficial serratus anterior plane with intercostal
injecting local anaesthetic above the serratus anterior nerves block performed by the surgeon (under direct
muscle, between it and the latissimus dorsi muscle vision). No basic analgesia was reported. They also found
(superficial serratus anterior plane block) or below the no significant difference in pain scores and postoperative
serratus muscle, between it and the intercostal muscles analgesic consumption.
(deep serratus anterior plane block). Four studies compared Li et al. [63] studied the use of different doses of
€
the serratus anterior plane block vs. no block. Okmen et al. dexmedetomidine (0.5 lg.kg-1 or 1 lg.kg-1) as an adjuvant
[54] concluded that pain scores were lower in the deep to ropivacaine in superficial serratus anterior plane block.

318 © 2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery Anaesthesia 2022, 77, 311–325

Basic analgesia was delivered with paracetamol and NSAIDs. mobilisation at 48 h. There was no difference in the
They reported significant lower pain scores in the high-dose occurrence of postoperative nausea and vomiting.
dexmedetomidine group (1 lg.kg-1), with reduced opioid Three studies compared thoracic epidural analgesia
consumption when compared with lower doses. with paravertebral block. Okajima et al. [70] compared
Comparisons were made between the serratus anterior thoracic epidural with paravertebral block catheter and
plane block and the ESP block in three different studies. found no difference in pain scores and opioid consumption.
Ekinci et al. [64] found lower pain scores and lower opioid All patients received NSAIDs. There was more hypotension
consumption in the ESP block group compared with deep in patients who received thoracic epidural. Yeap et al. [71]
serratus anterior plane block. Basic analgesia was provided compared thoracic epidural with paravertebral block
with NSAIDs only. Gaballah et al. [65] performed a superficial delivered in two methods. In the thoracic epidural group, an
serratus anterior plane block and found comparable results, infusion of bupivacaine 1.25 mg.ml-1 with hydromorphone
but they used both NSAIDs and paracetamol as rescue 0.05 mg.ml-1 was commenced postoperatively. In one
medication. Finnerty et al. [66] found no difference between paravertebral group, a single shot of 30 ml of ropivacaine
deep serratus anterior plane block and ESP block, both in 5 mg.ml-1 was injected through the catheter inserted before
analgesic effect and opioid consumption. Paracetamol and surgery. In the other paravertebral group, 10 ml.h-1 of
NSAIDs were given to both groups. ropivacaine 2 mg.ml-1 was administered continuously
A systematic review and meta-analysis by Zhang et al. through the same catheter. Basic analgesia consisted of pre-
[67] investigated whether peri-operative ultrasound-guided operative pregabalin and paracetamol followed by
serratus anterior plane block combined with general postoperative paracetamol. This study reported that
anaesthesia is more effective and safer than systemic thoracic epidural provided greater analgesia than both
analgesia after VATS. They included three randomised single-shot and continuous infusion paravertebral blocks.
controlled trials and one retrospective trial. They found that There was also less opioid consumption in the thoracic
peri-operative serratus anterior plane block reduced epidural group compared with the paravertebral block
postoperative pain scores and analgesic consumption after group. There was no difference in the incidence of chronic
general anaesthesia. Moreover, serratus anterior plane pain at 6 months between the groups. Huang et al. [72]
block provided better patient satisfaction. No significant compared thoracic epidural vs. ultrasound-guided
difference was found in duration of surgery, time to chest continuous paravertebral block performed either by a
tube removal, length of stay or side-effects. parasagittal or a transverse approach. All patients received
NSAIDs. Pain scores were lower in the thoracic epidural
Thoracic epidural analgesia group and a larger sensory block extension was obtained.
Seven studies investigated the use of thoracic epidural There was a high ratio of failure to identify the epidural space
analgesia for VATS. Zejun et al. [68] compared thoracic (14.6%) and hypotension in the thoracic epidural group and
epidural analgesia with i.v. sufentanil PCA in patients an even higher rate of failure of catheter placement in the
receiving NSAIDs as basic analgesia. In the thoracic epidural parasagittal paravertebral group (27.1%).
group, a bolus of 5 ml ropivacaine 2.5 mg.ml-1 solution was A review by Harky et al. [73] sought to compare thoracic
administered after catheter placement before surgery, epidural and paravertebral blocks for analgesia and
followed by a 5 ml.h-1 infusion of the same solution. postoperative complications. They included three small-
Postoperatively, patients in the thoracic epidural group randomised controlled trials and one small cohort study.
received ropivacaine 1.5 mg.ml-1 and sufentanil 0.2 lg.ml-1 From a pain perspective, there was no conclusive evidence
at a rate of 5–10 ml.h-1 with a bolus of 5 ml allowed every to recommend either thoracic epidural or paravertebral
40 min. They found superiority in pain control at rest and block: one study by Kashiwagi et al. [74] demonstrated
mobilisation in the thoracic epidural group. Epidural significantly lower levels of pain with thoracic epidural, one
analgesia was also associated with a reduced incidence of study by Kosinski et al. [75] showed better pain control with
nausea and vomiting and a shorter duration of paravertebral block and the third study by Okajima et al.
postoperative ileus. [70] found no difference between the two techniques.
Tseng et al. [69] compared thoracic epidural vs. i.v. Paravertebral block was associated with lower rates of
fentanyl PCA and low-dose ketamine. Basic analgesia was urinary retention and hypotension compared with thoracic
provided by intercostal nerves block performed by epidural.
surgeons. All patients received ketorolac. The authors did Hotta et al. [76] compared thoracic epidural with
not find any difference in pain scores at rest and during extrapleural blocks. Basic analgesia was provided with

© 2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. 319
Anaesthesia 2022, 77, 311–325 Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery

flurbiprofen. The authors found no significant difference in Discussion

analgesic effect and opioid consumption. Using the PROSPECT approach, we advise the
Lee et al. [77] showed that the addition of magnesium administration of a combination of paracetamol, NSAIDs or
100 mg to an epidural injection of ropivacaine did not a COX-2-specific inhibitor, pre-operatively or intra-
improve postoperative pain within the first 48 postoperative operatively, and continued in the postoperative period. The
hours and did not reduce opioid consumption. The primary benefits of these basic analgesics are well described for
outcome, chronic postoperative pain, did not differ other procedures [82, 83]. The benefit of the association of
between the two groups. NSAIDs and paracetamol is not demonstrated in the setting
of VATS but we consider that these are fundamental
Intercostal nerves block analgesics patients may receive and in addition it seems
Ahmed et al. [78] assessed the effect of single-shot inconceivable that patients received only rescue analgesia
intercostal nerves block performed at the end of the surgical in control groups when a new drug or analgesic technique is
procedure by the anaesthetist vs. no block. They reported assessed [10, 11]. Further, although there is no study
significantly lower pain scores in the intervention group, assessing the use of opioids on demand, the design of many
with less rescue analgesics required. Basic analgesia was studies highlights that patients need complementary on-
not reported. demand analgesia, commonly provided by an opioid, in
Zhang et al. [67] studied four different groups with addition to the study drug or technique.
different local anaesthetic mixtures used for intercostal nerves Pre-operative corticosteroids are routinely used in
blocks: ropivacaine plus perineural dexamethasone; other surgical procedures for their anti-emetic properties,
ropivacaine plus perineural dexmedetomidine; ropivacaine ability to increase the duration of the analgesic effect of
plus perineural dexmedetomidine and dexamethasone; and regional anaesthetic techniques and opioid-sparing effect.
a control group of plain ropivacaine. The study concluded that However, there is limited procedure-specific evidence for
the duration of analgesia was significantly longer in the the use of corticosteroids in VATS. Therefore, pre-operative
dexamethasone and dexmedetomidine group compared administration of i.v. corticosteroids is not recommended
with the other three groups. The duration of analgesia was due to the lack of specific evidence in the setting of VATS.
significantly shorter in the control group compared with the However, this does not mean that it contra-indicated
other three groups. There was no difference between the considering the benefits previously reported [84].
dexmedetomidine and the dexamethasone group. Maher We recommend intra-operative use of i.v.
et al. [79] compared an intercostal nerves block with dexmedetomidine because two studies documented that it
ropivacaine plus dexamethasone vs. plain ropivacaine. They reduces pain scores and opioid demand [12, 13].
reported a prolonged duration of analgesia in the intervention Dexmedetomidine also decreased the incidence of
group, with lower pain scores and reduced opioid postoperative agitation and cognitive dysfunction, and
requirements at 24 h. Paracetamol was given in both groups. postoperative nausea and vomiting [12–14]. An
improvement in lung function with an increase in FEV1 and
Subpleural block with catheter vital capacity has also been demonstrated [12, 13].
Ghee et al. [80] compared subpleural catheter with a Dexmedetomidine, which is an a2-adrenergic agonist, may
bupivacaine infusion inserted intra-operatively by the cause bradycardia and hypotension. In the studies
surgeon vs. intra-operative infiltration of the incision site reviewed, bradycardia and hypotension were observed at
with bupivacaine. There was no difference in the analgesic several time-points but did not prove to be clinically
effect. There was no significant difference in the two groups’ relevant. However, patients with severe cardiac disease,
usage of narcotics. Basic analgesia was achieved with conduction and/or rhythm disorders were excluded from
paracetamol and NSAIDs. these studies and dexmedetomidine should not be used in
that cohort of patients. On the contrary, postoperative i.v.
Surgical site infiltration dexmedetomidine is not recommended due to conflicting
Yang et al. [81] compared pre-emptive bupivacaine evidence and heterogeneous protocols. Reported side-
injection around the surgical incision vs. no block. There was effects (sedation; hypotension; bradycardia) were limited
no basic analgesia reported. There was no difference in but could lead to serious complications without proper
analgesic effect between groups and a higher need for monitoring. We found no effect of dexmedetomidine
rescue analgesia in the intervention group. administration on the incidence of chronic pain.

320 © 2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.
Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery Anaesthesia 2022, 77, 311–325

There are no studies comparing anaesthetic VATS due to its efficacy on pain control and limited side-
maintenance with or without opioid, and no study effects compared with thoracic epidurals. The use of a
dedicated to ‘opioid-free anaesthesia’ in VATS. Most studies catheter instead of single-shot analgesia prolongs the
used fentanyl or sufentanil for anaesthetic maintenance and analgesic effect but we do not recommend intermittent
rarely remifentanil. The benefits of remifentanil use (shorter bolus techniques compared with continuous infusions due
acting opioid effects and possibly faster recovery) should be to a lack of evidence [39, 40]. We also are unable to
balanced against the possible side-effects such as recommend a particular technique or approach to perform
hyperalgesia. However, this should be formally studied in this block, although catheter placement by the surgeon
well-designed trials. under direct supervision is easy to perform [42]. A pre-
Table 1 summarises the interventions that are not operative injection is also not recommended over
recommended for pain management in patients postoperative injection due to the lack of evidence.
undergoing VATS. We also recommend ESP blocks as several studies have
The addition of a regional analgesic technique as a shown the efficacy of ESP block vs. sham block [47, 48].
component of multimodal analgesia is strongly Compared with paravertebral block, two studies have
recommended, as VATS is otherwise associated with severe shown its non-inferiority and ESP block should therefore be
postoperative pain. The PROSPECT Group previously considered as an alternative. It could be more specifically
recommended the use of paravertebral block for indicated when the parietal pleural leaflet is damaged
thoracotomy. Paravertebral block is still recommended for precluding the efficacy of a paravertebral block with a
catheter.
The serratus anterior plane block is simple and quick to
Table 1 Analgesic interventions that are not recommended perform and side-effects are limited. The studies retrieved
for pain management in patients undergoing video-assisted considered a single injection and documented a benefit in
thoracoscopic surgery. terms of pain and opioid consumption compared with
Reason for not systemic basic analgesia or compared with infiltration of the
Intervention recommending incision site. Studies comparing the serratus anterior plane
Pre-operative and intra-operative block with the ESP block are not demonstrative enough to
Gabapentinoids Inconsistent evidence conclude the superiority of the latter, but reported a higher
Corticosteroids Lack of procedure-specific consumption of morphine in the former [54, 55]. Therefore,
evidence serratus anterior plane block cannot be considered as first-
Magnesium sulphate Limited procedure-specific line treatment until its efficacy compared with the more
evidence
established paravertebral and ESP blocks has been
Intravenous lidocaine Lack of procedure-specific
evidence confirmed by other studies. In addition, the possibility of

Transcutaneous electrical Inconsistent and limited

continuous catheter administration has not been evaluated.
nerve stimulation evidence If used, either a deep or a superficial injection can be
Wound infiltration Limited procedure-specific performed because there is currently no evidence of
evidence superiority of one over the other.
Intrapleural analgesia Limited procedure-specific Although there are no specific studies dedicated to this
evidence
point, the aforementioned chest wall fascial plane blocks
Intercostal nerves block Lack of procedure-specific
can be performed at a thoracic level adapted to the location
evidence
of the port sites, regardless of technique.
Thoracic epidural Non-inferiority of less
invasive techniques with Unlike previous PROSPECT recommendations for post-
fewer side-effects thoracotomy analgesia [5], we do not currently recommend
Postoperative thoracic epidural, even as a second-line option for VATS.
Gabapentinoids Inconsistent evidence Even if this technique provides adequate pain management,
Intravenous lidocaine Lack of procedure-specific it is a more invasive intervention than the peripheral nerve
evidence block techniques described above. It conveys the risks of
Dexmedetomidine Lack of procedure-specific hypotension, urinary retention and potential lower limb
evidence
weakness, which can delay early rehabilitation and
Transcutaneous electrical Inconsistent and limited
nerve stimulation evidence resumption of walking. In addition, there may be difficulties
in inserting the catheter or drug injection errors with serious

© 2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. 321
Anaesthesia 2022, 77, 311–325 Feray et al. | Guidelines for pain management after video-assisted thoracoscopic surgery

consequences. These complications make it inappropriate to Table 2 Overall recommendations for pain management
use thoracic epidurals when there are other alternatives. in patients undergoing video-assisted thoracoscopic
To prolong the duration and analgesic depth of surgery.

regional anaesthetic techniques, several adjuvants have Pre-operative and intra-operative

been administered in addition to local anaesthetic solutions. Paracetamol (Grade D)
The addition of preservative-free dexmedetomidine to local NSAID (Grade D)/COX-2-specific inhibitor (Grade D)
anaesthesia is recommended. It remains to be demonstrated Dexmedetomidine (excluding patient with severe cardiac
disease or conduction and/or rhythm disorders) (Grade B)
that a comparable effect could be achieved with i.v.
Postoperative
administration of dexmedetomidine making it more
Paracetamol (Grade D)
appropriate for clinical use.
The limitations of this review are those of the studies COX-2-specific inhibitor/NSAIDs (Grade D)

retrieved. Most studies had no systemic multimodal Opioid for rescue (Grade D)

analgesic strategies reported. Paracetamol and NSAIDs were Regional analgesia

not used as standard analgesia in many of the randomised Paravertebral block: single-shot (Grade A); continuous
(Grade A)
controlled trials. The sizes of control and intervention groups
Erector spinae plane block: single-shot (Grade A);
were commonly small and the studies were at a high risk of continuous (Grade B)
bias. There was significant heterogeneity between the Serratus anterior plane block: single-shot (Grade A);
studies regarding the methods of the study, the dosing continuous (Grade D)
regimens and administration. There was only qualitative
assessment and no quantitative analyses conducted. The
effect sizes were not highlighted and there was reliance on block can also be used to effectively reduce pain. In
statistical significance of included studies. combination with paracetamol and NSAIDs, opioids
There are further limitations regarding the outcomes of should still be used as rescue treatment in patients with
interest both in this current manuscript as well as those significant postoperative pain.
reported in included studies. In thoracic surgery,
accelerated rehabilitation is important. Postoperative Acknowledgements
outcomes are influenced by the patient’s ability to get out of SF and JL contributed equally to this manuscript and share
bed and participate in physical respiratory therapy first authorship. PROSPECT is supported by an unrestricted
exercises. However, very few studies had a primary grant from the European Society of Regional Anaesthesia
endpoint related to functional outcomes (e.g. time to and Pain Therapy (ESRA). In the past, PROSPECT has
resume walking; time to get out of bed; number of steps by received unrestricted grants from Pfizer Inc. New York, NY,
day; pain scores during physiotherapy). Only a few studies USA and Grunenthal, Aachen, Germany. GJ has received
looked at length of stay as secondary outcomes. Time in honoraria from Baxter and Pacira Pharmaceuticals. FB has
hospital and time to ambulation were rarely described. It is received honoraria from Grunenthal, The Medicine
known that thoracic surgery is associated with chronic pain Company, Abbott France and Nordic Pharma France. MVdV
[85]. However, few studies included chronic pain as an has received honoraria from Sintetica, Grunenthal, Vifor
outcome. Future studies, preferably with sufficient sample Pharma, MSD, Nordic Pharma, Janssen Pharmaceuticals,
sizes and using standardised protocols, should be assessed Heron Therapeutics and Aquettant. No other competing
to provide recommendations considering the safety profile interests declared.
of analgesic interventions.
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© 2021 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. 325