Received: 17 March 2023 Revised: 19 July 2023 Accepted: 8 August 2023

DOI: 10.1111/aas.14318

RESEARCH ARTICLE

Rebound pain and postoperative pain profile following brachial

plexus block compared to general anaesthesia—An
observational study

Ann-Kristin Schubert 1 | Thomas Wiesmann 1,2 | Christian Volberg 1 |

Jenny Riecke 3 | Alexander Schneider 1 | Hinnerk Wulf 1 | Hanns-Christian Dinges 1

1
Department of Anaesthesiology and Intensive
Care Medicine, University Hospital Marburg,
Philipps University of Marburg, Marburg,
Germany
2
Department of Anaesthesiology and Intensive
Care Medicine, Diakoneo Diak Klinikum
Schwäbisch-Hall, Schwäbisch-Hall, Germany
3
Department of Clinical Psychology and
Psychotherapy, Philipps University Marburg,
Marburg, Germany
Correspondence
Ann-Kristin Schubert, Department of
Anaesthesiology and Intensive Care Medicine,
University Hospital Marburg, Philipps
University Marburg, 35033 Marburg,
Germany.
Email: aschub@med.uni-marburg.de
Abstract
Background: Regional anaesthesia has the benefit of reducing the need for systemic
analgesia and therefore, potentially reducing undesired side effects. With the end of
the sensory nerve block however, many patients report severe pain that requires
therapy with opioids and often compromise the initial opioid sparing effect. This
study aimed to characterise the postoperative pain profile and the phenomenon of
rebound pain after axillary brachial plexus anaesthesia (RA) compared to general
anaesthesia (GA).
Design: Single-centre observational, stratified cohort study.
Setting: The study was conducted at University Hospital Marburg from May 2020
until September 2022.
Participants: One hundred thirty-two patients receiving elective hand and forearm
surgery were enrolled in this study.
Interventions: Group RA received ultrasound-guided brachial plexus anaesthesia via
the axillary approach with 30 mL of prilocaine 1% and 10 mL ropivacaine 0.2%.
Group GA received balanced or total intravenous general anaesthesia.
Main Outcome Measures: Primary endpoint were integrated pain scores (IPS) within
24 h postoperatively. Secondary endpoints were pain scores (NRS 0–10), morphine
equivalents, patient satisfaction, quality of recovery and opioid-related side effects.
Results: One hundred thirty-two patients were analysed of which 66 patients received
brachial plexus block and 66 patients received general anaesthesia. Following RA sig-
nificantly lower IPS were seen directly after surgery (p < .001) and during the post-
anaesthesia care unit interval (p < .001) but equalised after 3 h at the ward. No over-
shoot in pain scores or increased opioid consumption could be detected. Patient satis-
faction and postoperative recovery were comparable between both groups.
Conclusion: The IPS and NRS was initially lower in the RA group, increased with fad-
ing of the block until equal to the GA group and equal thereafter. Although various
definitions of rebound pain were met during this phase, the opioid sparing effect of
regional anaesthesia was not counteracted by it. The incidence of episodes with

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© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

Acta Anaesthesiol Scand. 2023;1–9. wileyonlinelibrary.com/journal/aas 1

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2 SCHUBERT ET AL.

uncontrolled, severe pain did not differ between groups. We found no clinical impli-
cations of rebound pain in this setting, since the RA group did not show higher pain
scores than the GA group at any time point.
Trial Registration: German Clinical Trials Register (DRKS00021764).

KEYWORDS
brachial plexus block, peripheral nerve block, postoperative pain, rebound pain, regional
anaesthesia

Editorial Comment
In this stratified observational study comparing brachial plexus block to general anaesthesia, a
significant reduction in pain and opioid consumption was observed in the post-anaesthesia care
unit (PACU) and the first 3 h at the ward. Importantly, no signs of rebound pain were observed
in the brachial plexus group at any timepoint. These findings support the use of brachial plexus
block for lower arm surgery and potentially early PACU discharge or bypass as the next step.

1 | I N T RO DU CT I O N and its impact on the opioid sparing effect of peripheral regional

Rebound pain is a clinical phenomenon that is associated with fading
of sensory block after regional anaesthesia.1 Patients affected by this
describe it as a very noticeable and sudden increase in pain that
requires immediate analgesic treatment. This raises the question how
much the opioid sparing effect of regional anaesthesia is counteracted
by the phenomenon of rebound pain and might result in poorer qual-
ity of recovery after surgery.
Different authors have tried to characterise rebound pain further
and it has become a topic of interest in recent literature on analgesic
quality. A clear definition of rebound pain is still missing. Some authors
like Barry, Hamilton and others propose a definition via an increase in
pain from NRS <3 to NRS >7,2,3 while Dada et al. define the phenome-
non by the time and interval, in which the pain occurs.4 Yet, most
authors that reported rebound pain in the past have not given a defini-
tion other than severe pain or a quantifiable increase in pain associated
with fading of the block.5–7 To assess postoperative pain and analgesia
quality, different effect measures have been proposed. Raw pain scores
(NRS 0–10) and morphine equivalents (MEQ) are the most common
measures in pain studies. These endpoints are easily comprehensible;
however, when interpreted separately, they can be misleading because
differences in MEQ consumption can nullify differences in pain scores
and vice versa. To overcome this and enhance the precision at which
differences in analgesic quality can be detected, composite outcomes
like integrated pain scores (IPS) have been proposed.8
Composite endpoints are particularly useful when investigating
postoperative pain profiles and the phenomenon of rebound pain,
9
which has been conducted by Sort et al. characterising rebound pain
following foot and ankle surgery under spinal anaesthesia versus pop-
liteal sciatic nerve block.
The aim of our observational study is to characterise the pain pro-
files and analgesic quality after brachial plexus anaesthesia compared
to general anaesthesia for hand and forearm surgery. Furthermore, we
wanted to investigate the incidence and relevance of rebound pain
anaesthesia.
2 | METHODS
2.1 | Reporting
According to the recommendations of the EQUATOR network
(Enhancing the Quality and Transparency of Health Research), the guide-
line for observational studies STROBE (The Strengthening the Reporting
of Observational Studies in Epidemiology Statement)10 was followed.
The completed checklist can be found in the supplemental content.
2.2 | Study approval
Ethical approval for this study (Ethical Committee N 24/20) was pro-
vided by the Ethical Committee at University Hospital Marburg, Mar-
burg, Germany (Chairperson C. Seifart) on 13 March 2020.
2.3 | Study registration
This study followed the Declaration of Helsinki and was prospectively
registered on 15 May 2020 in the German Clinical Trials Register
(DRKS00021764). Written informed consent was obtained from all
subjects participating.
2.4 | Study design
This single-centre, observational, stratified cohort study was con-
ducted at University Hospital Marburg from May 2020 until
September 2022.

SCHUBERT ET AL.
2.5 | Sample size calculation
The sample size calculations for this observational study were based
on preliminary studies that examined pain levels expressed as IPS and
the incidence of rebound pain after peripheral nerve block.1,9,11 The
goal was to detect a 30% difference in IPS, pain score and/or con-
sumption of morphine equivalents, which resembles a NRS difference
of 1.5–2 depending on the mean. Assuming a power of 80% in a two-
tailed test at a level of significance of 0.05, a total number of
90 patients were calculated. To account for potential drop-outs, a
total of 110 patients were required.
Sample size calculation was performed using G*Power
software.12
2.6 | Eligibility
Adult patients ASA status I-IV undergoing elective surgery on the
hand, wrist and forearm under either brachial plexus block or general
anaesthesia were eligible for this observational study.
Exclusion criteria were age under 18 years, inability, or unwilling-
ness to give consent, pregnancy, presence of infection at injection
site, presence of pre-existing central and peripheral neurological dis-
ease, pre-existing coagulopathy, and known or suspected allergy to
local anaesthetics.
2.6.1 | Recruitment
In absence of severe cardiopulmonary comorbidity, peripheral regional
anaesthesia and general anaesthesia are considered equally viable for
surgery of the hand and forearm at our institution. Written informed
consent to the individually preferred anaesthesia was obtained from
patients before informing them about the study. After written
informed consent to also participate in the observation was obtained,
the patients were enrolled. Towards the end of reaching the sample
size with this intention-to-treat recruitment manner, the demographi-
cal differences between groups were too inhomogeneous to answer
the research question. An amendment was made to the hospital ethics
committee to recruit 30 additional patients and to switch to a strati-
fied recruitment to even out the demographic differences. During
stratified recruitment, patients still chose their individually preferred
type of anaesthesia, but were only asked to participate in the study, if
they happened to be of the underrepresented gender and had chosen
the underrepresented type of anaesthesia.
2.7 | Peripheral nerve block
We used an axillary approach to the brachial plexus for regional
anaesthesia group.
In the induction area, standard monitoring was applied, and
patients were placed in the supine position. All peripheral nerve
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3
blocks were ultrasound guided (S-Series; Sonosite, Bothell,
Washington, USA) and performed by anaesthetists with basic experi-
ence in regional anaesthesia. Nerve stimulation (HNS12; B. Braun, set
at 2 Hz, 0.1-ms pulse duration, target current 0.5 to 1.0 mA) was used
for additional verification of final tip position.
Peripheral nerve block was conducted with 30 mL 1% prilocaine
to which 10 mL 0.2% ropivacaine were added for longer block dura-
tion, according to the local standard.
2.8 | General anaesthesia
General anaesthesia was induced using intravenous propofol 2–
3 mg
kg 1
and intravenous fentanyl 2–3 μg
kg 1
according to local
standards. Insertion of either a laryngeal mask or an endotracheal tube
after intravenous rocuronium 0.5–0.6 mg
kg 1
was at the discretion
of the anaesthetist in charge. Balanced or total intravenous anaesthe-
sia was maintained with desflurane or propofol (target bispectral index
values between 35 and 55) and intermittent fentanyl as required.
2.9 | Postoperative pain therapy
Standard basic postoperative analgesia protocol included ibuprofen
and metamizole or paracetamol as basic analgesia as follows: ibupro-
fen 600 mg QDS (four times daily), metamizole 1000 mg QDS or para-
cetamol 1000 mg QDS. For rescue analgesia patients received
oxycodone + naloxone combination and/or intravenous morphine or
piritramide on demand, following local standard operating procedures
for postoperative pain.
2.10 | Data collection
Baseline data and patient characteristics (age, sex, weight, ASA physi-
cal status) were collected pre-operatively.
To examine the full timespan in which rebound pain is likely to
occur after fading of peripheral regional anaesthesia, 24 h postopera-
tively were chosen for assessment.1,9
Patients were asked on current pain score 24 h postoperatively
on a 0–10 numeric rating scale (NRS) and cumulative opioid and non-
opioid consumption were reported.
For longitudinal pain assessment patients registered pain scores
on a NRS from 0 to 10 for the first 24 h postoperatively at 3-h
intervals.
At 24 h postoperatively patients answered questionnaires on sat-
isfaction, quality of recovery (German QoR-15 and Global Surgical
Recovery Index, GSR) on a 0–100 NRS. Opioid-related side effects
were assessed using the German version of the opioid-related symp-
tom distress scale (OR-SDS).
For missing data in longitudinal repeated measures, the last
observation was carried forward. For missing data in single measures,
the respective case was excluded from calculations.
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4 SCHUBERT ET AL.

2.11 | Follow-up 2.13 | Secondary endpoints

All patients received a telephone call on postoperative Day 7 with a Secondary endpoints were:
questionnaire on actual pain scores, functional status and potential
adverse events. For long-time follow-up assessment patients were • Mean pain scores on a numeric rating scale (0–10) registered
contacted by phone 3 months after surgery to obtain actual pain within the first 24 h in 3-h intervals
score, satisfaction and quality of recovery (QoR-15, GSR). Patients not • Cumulative morphine equivalent consumption 24 h
available for telephone interview were called each day for up to postoperatively
5 days and were then excluded from analysis as lost to follow-up. • Patient satisfaction, adverse events and opioid-related site-effects
(OR-SDS), quality of postoperative recovery (GSR)

2.12 | Primary endpoint
Primary endpoint were differences in the IPS over the course of 24 h
postoperatively, measured in 3-h intervals. IPS were calculated from
reported pain scores and cumulative morphine equivalents (MEQ) tak-
ing into account any higher MEQ requirements to achieve comparable
analgesia (equi-analgesia) as proposed by Silverman et al.8
IPS were calculated as the deviation from mean rank in pain score
added to deviation from mean rank in MEQ using Microsoft Excel,
resulting in an individual score for each participant between 200%
and +200% (the higher the pain score and the higher the opioid con-
sumption, the higher the IPS-Score).
Opioid-related side effects were reported as incidence of clini-
cally meaningful events (CME) assessed with the German OR-SDS as
proposed by Chan et al.13
Patient satisfaction was assessed on a 0–10 NRS (very dissatis-
fied to very satisfied).
2.14 | Statistical analysis
Statistical analysis was performed using SPSS version 27.0 (SPSS Inc.,
Chicago, Illinois, USA) and Microsoft Excel for Mac Version 16.43
(Microsoft Corporation, Redmond, Washington, USA).

Enrollment Patients with forearm/hand

surgery from May 2020 to
January 2021 (n= 195)
and from May 2022 to
September 2022 (n=46)

Excluded (n= 101)

¨ Declined to participate
¨ Did not meet inclusion criteria
¨ Other reasons

Allocation

Patients enrolled in the study

(n=140)

Allocated to regional anesthesia (n= 74) Allocated to general anesthesia (n= 66)
¨ Conversion to general anesthesia due to
insufficient block (n= 6)
¨ Local infiltration instead of regional
anesthesia (n=1)
¨ Regional and general anesthesia (n=1)

Analysis

Analysed for primary endpoint (n= 66) Analysed (n= 66)

¨ Secondary endpoint (n= 65)

FIGURE 1 CONSORT-flow chart of the inclusion process.

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SCHUBERT ET AL. 5

Patient characteristics are presented as mean (SD) or number (%) 3 | RE SU LT S

unless otherwise stated as a standard normal distribution was
assumed for patient characteristics. 3.1 | Enrolment
For pain scores, MEQ and integrated scores standard normal dis-
tribution was tested via Normal-Q-Q-Plots. p < .05 was considered Over the duration of recruitment, a total number of 241 patients were
statistically significant. scheduled for elective surgery on the hand, wrist, or forearm.
One hundred ten patients were recruited via convenience sam-
pling method. The patient characteristics of the cohorts were inhomo-
TABLE 1 Patient characteristics. geneous regarding cohort size and sex distribution. As the general

General
anaesthesia group was underpowered based on the sample size calcu-
Axillary brachial anaesthesia, lation, an amendment was applied to proceed with stratified recruit-
plexus block, n = 66 n = 66 ment of 30 additional patients.
Age in years, mean ± SD 40 ± 16 40 ± 16 In total, 140 patients met the inclusion criteria and gave written
BMI (kg m 2
), mean 27 ± 7 26 ± 4 informed consent to be included in the study. Eight patients were
± SD excluded from data analysis: one patient due to requiring surgical infil-
Sex (male/female) 46/20 51/15 tration instead of regional anaesthesia and one patient because of
ASA physical status 41/18/7 31/31/4 receiving a supplemental supraclavicular block in combination with
(n = I/II/III) general anaesthesia and six patients due to insufficient nerve block
Duration of surgery in 48 ± 29 56 ± 45 requiring conversion to general anaesthesia. One hundred thirty-two
minutes, mean ± SD patients were included in final data analysis for primary endpoint.
Type of surgery The regional anaesthesia group had 66 patients; the general anaes-
Osteosynthesis 35 39 thesia group had 66 patients. The inclusion process is shown in Figure 1.
Soft tissue surgery 24 18
Arthroscopy 0 2
Removal of 7 7 3.2 | Patient characteristics
osteosynthesis
Use of intraoperative 56 60 Patient characteristics, details of anaesthesia techniques and surgical
Pneumatic tourniquet procedures of included patients are presented in Table 1.
Note: Patient characteristics by study group. Data are presented as mean Both groups were comparable regarding age, body mass index
± SD (standard deviation) and n. (BMI), ASA physical status, duration and type of surgery.

F I G U R E 2 Integrated pain scores

(mean ± SD) over 24 h after upper limb
surgery per group. General compared with
regional anaesthesia.
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6 SCHUBERT ET AL.

F I G U R E 3 Mean pain scores (mean

± SD) over 24 h after upper limb surgery
on a 0–10 numeric rating scale (NRS) per
group. General compared with regional
anaesthesia.

Normal Distribution of the data was verified via Q-Q Plot for pri- interval was seen in 45 patients with regional anaesthesia, and
mary endpoint (Supplemental Digital Content 1). 30 patients following general anaesthesia.6 Transitions from well-
controlled pain (≤3) to uncontrolled and strong pain (≥7) were seen in
13 (RA) and 13 (GA) patients.2
3.3 | Primary endpoint

3.3.1 | Integrated pain scores 3.4.3 | Postoperative cumulative morphine

The IPS following Silverman et al. are shown in Figure 2. Statistically
significant differences between the groups were seen at the PACU
( p < .001) and at transfer to the ward (Figure 2, ward 0 h, p < .001).
During the first 6 h at the ward, the IPS of the groups had equalised.
The mean IPS over 24 h was 8.87 (SD 48.06) in the RA group and
8.87 (SD 67.18) in the GA group (not significant, p = .08).
equivalents
Postoperative cumulative morphine equivalents per group are shown
in Figure 4. Cumulative morphine consumption at PACU was signifi-
cantly lower in RA group (0.15 mg, SD 0.97) compared with GA group
(4.62 mg, SD 5.63) ( p < .001). Cumulative morphine consumption at
ward was comparable between the RA group (2.54 mg, SD 8.08) and
the GA group (2.20 mg, SD 5.83).

3.4 | Secondary endpoints

3.4.4 | Quality of recovery and patient
3.4.1 | Pain scores at group level satisfaction

Mean pain scores over 24 h are shown in Figure 3. Significant differ-
ences for pain scores were seen directly postoperative during the
PACU interval ( p < .001) and for timepoint 0 h at the ward (p < .001)
in favour of the RA group.
3.4.2 | Individual pain scores
According to the two most common definitions of rebound pain,2,6 a
quantifiable increase in pain (>2) during the postoperative time
Global surgery recovery rated on a 0–10 NRS was 6.1 (SD 2.1) in the
RA group and 5.7 (2.4) in the GA group showing no statistical
significance.
Quality of recovery assessed on the QoR-15 was 113.3 (SD 15.1)
in RA group compared with 109.8 (19.0) in GA group without statisti-
cal significance.
Patient satisfaction on a 0–10 NRS was comparable in either
group (mean score of 8.6 [SD 2.1] in the RA group and 8.3 [SD 2.8] in
the GA group).
Results for secondary endpoints are reported in Table 2.
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SCHUBERT ET AL. 7

F I G U R E 4 Postoperative morphine
equivalents (mean ± SD) for separate
timepoints (PACU, ward) per group.
General compared with regional
anaesthesia.

TABLE 2 Secondary endpoints.

Regional General
anaesthesia anaesthesia Statistical
Secondary endpoints (n = 66) (n = 66) p-Value test
Cumulative postoperative morphine i.v. equivalents 24 h; mg 3±9 7 ± 10 .01* t-test
Pain score AUC 0–24 h 7.3 ± 4.5 8.3 ± 5.6 .25 t-test
Quality of recovery, (QoR-15) 113 ± 15 110 ± 19 .24 t-test
Opioid adverse effects, CME ≥ 1 16 (24) 14 (21) .34 χ2
Patient satisfaction (NRS 0–10) 8.6 ± 2.1 8.3 ± 2.8 .6 t-test
Would recommend type of anaesthesia (NRS 0–10) 8.95 ± 2.0 8.82 ± 2.5 .79 t-test
Global surgery recovery (NRS 0–10) 6.1 ± 2.1 5.7 ± 2.4 .28 t-test

Note: Summary of secondary endpoints. Data presented as mean ± SD or number (n) with percentage (%).
*p < .05.

3.4.5 | Opioid-related side effects (OR-SDS)
Opioid-related side effects were reported as critical meaningful event
(CME) on the German OR-SDS. Side effects with at least one CME
were comparable and observed by 16 patients (24.24%) in the RA
Group compared to 14 patients (21.21%) in the GA group (Table 2).
Opioid-related adverse event rates are presented in Supplemental
Digital Content 2.
3.5 | Follow-up
The 7-day and 3-months follow-up of the patients showed no statisti-
cally significant differences in pain chronification or pain profiles. No
serious adverse events occurred during the follow-up period (see Sup-
plemental Digital Content 3; Tables 1 and 2).
4 | DI SCU SSION
In the present study, we examined the pain profile in a multimodal
analgesia environment following hand and forearm surgery under gen-
eral versus brachial plexus anaesthesia. Our goal was to quantify the
pain associated with fading of the plexus block, which has previously
been described as rebound pain.
From a methodological point of view, the chosen endpoints (IPS,
pain scores and MEQs) are adequate tools to detect differences in the
quality of analgesia between study populations in a comprehensible

8 SCHUBERT ET AL.
fashion, while reporting the raw pain scores and the total morphine
equivalents maintains the transparency and traceability for the
clinician.
The patient population of young adults with predominantly bony
surgery in the ambulatory setting receiving a single injection brachial
plexus anaesthesia is at the highest risk of developing rebound pain
2,14,15
according to the existing literature.
Our study revealed a statistically significant difference in IPS and
pain scores during the PACU time interval and during the first 3 h at
the ward in favour of the regional anaesthesia group. During the first
6 h, the regional anaesthesia group showed an increase in pain scores
of >2 on the NRS, after which it levelled with the general anaesthesia
group (Figure 3).
Regarding the patient-centred endpoints, patients rated both
anaesthesia techniques equally and highly satisfactory.
The initial difference in pain scores could in fact be described as
rebound pain following the definition of Williams et al.,6 since a differ-
ence of >2 can be assumed to be quantifiable according to the com-
16,17
mon definitions of Cepeda and Farrar.
However, apart from this definition being matched, we could not
see any of the clinical implications that have brought the phenomenon
of rebound pain to such a high interest in the scientific debate. The
pain score did not overshoot the GA group at any time point and
the initial morphine sparing effect of the RA was not counteracted by
this at all, which can clearly be seen from the IPS curve (Figure 2) and
is the reason why the IPS is the ideal tool to detect rebound pain.
If we cannot detect rebound pain at group level in the pain scores
and morphine equivalents, the question remains, whether it is a rele-
vant problem for individual patients. Regarding the definition of Barry
et al.,2 describing the transition of well-controlled to uncontrolled,
severe pain, rebound pain occurred exactly 13 times in each of our
groups. The term rebound pain which implies an overshoot in pain
and related to fading of regional anaesthesia, is therefore not suitable
to describe our observations on brachial plexus anaesthesia.
The scientific debate on rebound pain originated from the differ-
ences between general and regional anaesthesia. Unfortunately, only
few studies have compared the pain profiles of these two further.
Galos et al.14 for example could not detect clinically relevant differ-
ences in the pain profiles following brachial plexus RA.
Other recent studies that have described postoperative pain pro-
files but only compared different approaches of regional anaesthesia, for
example, the addition of adjuvants as dexamethasone or ketamine, con-
cluded that the incidence of rebound pain is 50%–70% in peripheral
nerve blocks of brachial, lumbar and sacral plexus and that it has strong
implications for clinical practice.2,9,15,18–20 Yet, they did not compare it
to general anaesthesia anymore. But since episodes of uncontrolled pain
occur during recovery from general anaesthesia as well, a study design
that does not include this control group may not be suitable to estimate
the true incidence of rebound pain. And therefore, it is arguable that
these studies actually describe clinically relevant rebound pain.
Limitations of the present study are the observational design,
which of course provides a lower quality of evidence than a random-
ised trial would do.
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We initially recruited patients by convenience sampling, however,
as the resulting study groups would be too inhomogeneous to answer
the research question. The GA group included primarily women and
was underpowered in size and the RA group was larger than required
and included primarily men. We decided to proceed with an observa-
tional but stratified recruitment regarding group size and sex distribu-
tion. The resulting groups were therefore homogeneous regarding
these aspects. Since the enrolment to the study was still only offered
to patients that had already decided on their type of anaesthesia, the
study design remained entirely observational in this process and nei-
ther of the groups was biased by this. A demographic difference that
we did not stratify remains in the distribution of surgical procedures
(Table 1). More patients in the GA group received an osteosynthesis,
which is expected to be rather painful, while soft tissue surgery, which
is considered less painful was slightly underrepresented in this group.
This inhomogeneity is a limitation and with a randomised study
design, the GA group may have had slightly less pain than we
observed here.
If we assume that demographic differences affect the occurrence
of the phenomenon rebound pain, it is important to look into the
intention-to-treat distribution of risk factors or groups at risk for
higher sensation of pain. These distributions may differ across other
institutions and populations and may explain, why rebound pain or
other phenomenons are noticeable in a clinical setting or not. If popu-
lations at risk for an unwanted event tend to already choose the
favourable intervention by themselves, the effect of the ‘worse’ inter-
vention may be masked in the daily routine. If an effect only occurs in
the setting of controlled trials, it may drive a scientific debate on
something that cannot have more clinical implications than to aim for
the demographic distribution that is already natural.
Multiple testing was the case for the families of hypotheses
regarding IPS and raw pain scores. However, this was not considered
problematic because the described differences were detected with
high statistical significance, which would hold against a Bonferroni
correction of for 10 tests and a new level of statistical significance
of p < .005.
5 | CONC LU SION
Statistically significant differences in IPS were observed within the
early postoperative period. The IPS following brachial plexus block
levelled the general anaesthesia group after 6 h at ward, without
counteracting the initial opioid sparing effect. According to various
definitions, rebound pain could be detected in this trial, however, the
clinical implications of it were minor. Uncontrolled, severe pain
occurred equally often in either group.
AUTHOR CONTRIBU TIONS
Concept and design: Hanns-Christian Dinges, Ann-Kristin Schubert,
Jenny Rieke, Christian Volberg, Thomas Wiesmann and Hinnerk Wulf.
Study planning: Hanns-Christian Dinges, Ann-Kristin Schubert, Jenny
Rieke, Christian Volberg, Thomas Wiesmann and Hinnerk Wulf.

SCHUBERT ET AL.
Conduction and data acquisition: Alexander Schneider. Statistical analy-
sis: Hanns-Christian Dinges and Ann-Kristin Schubert. Data interpreta-
tion: Hanns-Christian Dinges, Ann-Kristin Schubert, Thomas
Wiesmann and Hinnerk Wulf. Drafting of the manuscript: Ann-Kristin
Schubert and Hanns-Christian Dinges. Revision and approval of the
manuscript: Hanns-Christian Dinges, Ann-Kristin Schubert, Thomas
Wiesmann and Hinnerk Wulf.
ACKNOWLEDGEMEN TS
The authors thank all clinical and research staff members of the
Department of Anaesthesiology and Intensive Care Medicine at
Philipps-University Marburg for their assistance with patient recruit-
ment and premedication.
FUND ING INFORMATION
This study was not funded by any external source. Only institutional
funds were used in this project.
CONF LICT OF IN TE RE ST ST AT E MENT
Thomas Wiesmann has received honoraria for lectures from Pajunk,
Vygon, Teva ratiopharm. Hinnerk Wulf has received honoraria for lec-
tures from Sintetica and Grünenthal. All other authors declare that
they have no conflict of interest.
DATA AVAI LAB ILITY S TATEMENT
The data was collected during the study period and is presented in
the manuscript.
ORCID
Ann-Kristin Schubert https://orcid.org/0000-0001-6712-3812
RE FE R ENC E S
1. Sort R, Brorson S, Gogenur I, Nielsen JK, Moller AM. Rebound pain
following peripheral nerve block anaesthesia in acute ankle fracture
surgery: an exploratory pilot study. Acta Anaesthesiol Scand. 2019;
63(3):396-402.
2. Barry GS, Bailey JG, Sardinha J, Brousseau P, Uppal V. Factors associ-
ated with rebound pain after peripheral nerve block for ambulatory
surgery. Br J Anaesth. 2021;126(4):862-871.
3. Hamilton DL. Rebound pain: distinct pain phenomenon or nonentity?
Br J Anaesth. 2021;126(4):761-763.
4. Dada O, Gonzalez Zacarias A, Ongaigui C, et al. Does rebound pain
after peripheral nerve block for orthopedic surgery impact postopera-
tive analgesia and opioid consumption? A narrative review. Int J Envi-
ron Res Public Health. 2019;16(18):3257.
5. Lavand'homme P. Rebound pain after regional anesthesia in the
ambulatory patient. Curr Opin Anaesthesiol. 2018;31(6):679-684.
6. Williams BA, Bottegal MT, Kentor ML, Irrgang JJ, Williams JP.
Rebound pain scores as a function of femoral nerve block duration
after anterior cruciate ligament reconstruction: retrospective analysis
of a prospective, randomized clinical trial. Reg Anesth Pain Med. 2007;
32(3):186-192.
7. Williams BA. Forecast for perineural analgesia procedures for ambula-
tory surgery of the knee, foot, and ankle: applying patient-centered
paradigm shifts. Int Anesthesiol Clin. 2012;50(1):126-142.
13996576, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/aas.14318 by Tunisia Hinari NPL, Wiley Online Library on [05/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
9
8. Silverman DG, O'Connor TZ, Brull SJ. Integrated assessment of pain
scores and rescue morphine use during studies of analgesic efficacy.
Anesth Analg. 1993;77(1):168-170.
9. Sort R, Brorson S, Gögenur I, et al. Peripheral nerve block anaesthesia
and postoperative pain in acute ankle fracture surgery: the AnAnkle
randomised trial. Br J Anaesth. 2021;126(4):881-888.
10. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,
Vandenbroucke JP. The Strengthening the Reporting of Observa-
tional Studies in Epidemiology (STROBE) statement: guidelines for
reporting observational studies. Lancet. 2007;370(9596):1453-1457.
11. Sort R, Brorson S, Gogenur I, Moller AM. AnAnkle Trial study proto-
col: a randomised trial comparing pain profiles after peripheral nerve
block or spinal anaesthesia for ankle fracture surgery. BMJ Open.
2017;7(5):e016001.
12. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statis-
tical power analysis program for the social, behavioral, and biomedical
sciences. Behav Res Methods. 2007;39(2):175-191.
13. Chan KS, Chen WH, Gan TJ, et al. Development and validation of a
composite score based on clinically meaningful events for the opioid-
related symptom distress scale. Qual Life Res. 2009;18(10):1331-
1340.
14. Galos DK, Taormina DP, Crespo A, et al. Does brachial plexus block-
ade result in improved pain scores after distal radius fracture fixation?
A randomized trial. Clin Orthop Relat Res. 2016;474(5):1247-1254.
15. Holmberg A, Hassellund SS, Draegni T, et al. Analgesic effect of
intravenous dexamethasone after volar plate surgery for distal radius
fracture with brachial plexus block anaesthesia: a prospective,
double-blind randomised clinical trial. Anaesthesia. 2020;75(11):1448-
1460.
16. Cepeda MS, Africano JM, Polo R, Alcala R, Carr DB. What decline in
pain intensity is meaningful to patients with acute pain? Pain. 2003;
105(1–2):151-157.
17. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical
importance of changes in chronic pain intensity measured on an
11-point numerical pain rating scale. Pain. 2001;94(2):149-158.
18. Fang J, Shi Y, Du F, et al. The effect of perineural dexamethasone on
rebound pain after ropivacaine single-injection nerve block: a ran-
domized controlled trial. BMC Anesthesiol. 2021;21(1):47.
19. Morita S, Oizumi N, Suenaga N, Yoshioka C, Yamane S, Tanaka Y.
Dexamethasone added to levobupivacaine prolongs the duration of
interscalene brachial plexus block and decreases rebound pain after
arthroscopic rotator cuff repair. J Shoulder Elbow Surg. 2020;29(9):
1751-1757.
20. Woo JH, Lee HJ, Oh HW, Lee JW, Baik HJ, Kim YJ. Perineural dexa-
methasone reduces rebound pain after ropivacaine single injection
interscalene block for arthroscopic shoulder surgery: a randomized
controlled trial. Reg Anesth Pain Med. 2021;46(11):965-970.
SUPPORTING INF ORMATION
Additional supporting information can be found online in the Support-
ing Information section at the end of this article.
How to cite this article: Schubert A-K, Wiesmann T,
Volberg C, et al. Rebound pain and postoperative pain profile
following brachial plexus block compared to general
anaesthesia—An observational study. Acta Anaesthesiol Scand.
2023;1‐9. doi:10.1111/aas.14318