titolo breve: TRAMADOL AND 0.5% LEVOBUPIVACAINE FOR SINGLE-SHOT
COPYRIGHT 2012 EDIZIONI MINERVA MEDICA O R I G I N A L A R T I C L E
Tramadol and 0.5% levobupivacaine for single-shot
interscalene block: effects on postoperative analgesia
in patients undergoing shoulder arthroplasty
F. ALEMANNO 1, D. GHISI 2, A. FANELLI 2, A. FALIVA 3,
B. PERGOLOTTI 3, F. BIZZARRI 3, G. FANELLI 3
1Department of Anesthesia and Pain Therapy, Ospedale San Camillo, Brescia, Italy; 2Department of Anesthesia and Pain
Therapy; Istituti Ospitalieri di Cremonaz Cremona, Italy; 3Department of Anesthesia, Intensive Care and Pain Therapy;
Background. The aim of this study was to evaluate the efficacy of tramadol as an adjuvant to the local anaesthetic
solution in patients undergoing shoulder arthroscopy for rotator cuff tear after middle interscalene block (MIB). Methods. We enrolled 120 patients (ASA I-II), scheduled for arthroscopic surgery for rotator cuff tear. The patients
were sedated with midazolam 0.02 mg/kg and haloperidol 2 mg i.v. before performing MIB. All subjects underwent
a MIB with 0.4 mL/kg of 0.5% levobupivacaine. After computerized randomization, all patients were allocated in
1 of 3 groups, each including 40 subjects. Group Placebo (Group P) received 0.4 mL/kg of 0.5% levobupivacaine
plus isotonic sodium chloride for MIB and isotonic sodium chloride i.m. Group “Perineural Tramadol” (Group TPN)
received 0.4 ml/Kg of 0.5% levobupivacaine plus 1.5 mg/kg of tramadol perineurally and isotonic sodium chloride
i.m. Group “Intramuscular Tramadol” (Group TIM) received 0.4 ml/Kg of 0.5% levobupivacaine plus isotonic so-
dium chloride perineurally and 1.5 mg/kg of tramadol i.m. Results.
The MIB onset times were not statistically different in the three groups. The duration of analgesia was
significantly longer in Groups TPN and TIM, where tramadol was administered, either i.m. or perineurally, compared
with the placebo group. A significant statistical difference was found in the duration of analgesia between the group
Conclusion. The addition of tramadol to the local anaesthetic solution administered for MIB provided a longer
duration of analgesia compared with placebo and i.m tramadol administration in patients undergoing arthroscopic
surgery for rotator cuff tear. (Minerva Anestesiol 2012;78:291-96)Key words: Tramadol - Postoperative period - Analgesia.
No additional reproduction is author.
Shoulder arthroplasty is related to severe pain longed analgesia, use of additives has been often
in the postoperative period.1 Interscalene bra-
proposed for peripheral nerve blocks to improve
chial plexus block provides adequate postopera-
quality and duration of anesthesia and postop-
tive analgesia, reducing time-to-home discharge erative pain relief.7
in patients undergoing one-day surgery.2, 3 The
The direct action of opioid analgesics such as
efficacy of a middle approach to the interscalene morphine, fentanyl and sufentanil on the pe-
block for the brachial plexus has been already de-
ripheral nervous system are still debated, but
buprenorphine and tramadol seem to pass the
Although peripheral nerve blocks with long-
neuronal membrane and diffuse within the in-
acting local anesthetics (LA) can provide pro-
terstitial or axonal fluid as lipophylic drugs.8, 9
COPYRIGHT 2012 EDIZIONI MINERVA MEDICA
TRAMADOL AND 0.5% LEVOBUPIVACAINE FOR SINGLE-SHOT INTERSCALENE BLOCK
Tramadol has been also proven to have a cen-
(0.03 mL/kg) and the i.m. isotonic sodium chlo-
tral analgesic effect due to its monoaminergic ride (0.03 mL/kg);
and m-receptor agonistic activity, together with
some peripheral local anesthetic properties with ceived the anesthetic mixture containing 0.4 ml/
low incidence of serious adverse events.10, 12 Ani-
Kg of 0.5% levobupivacaine plus tramadol (1.5
mal investigations have shown effects of trama-
mg/kg) and the i.m. isotonic sodium chloride
dol on the uptake and release of norepinephrine (0.03 mL/kg);
3) group intramuscular tramadol (Group TIM)
The aim of this prospective, randomized, dou-
received the anesthetic mixture containing 0.4
ble-blinded study was to evaluate the efficacy of ml/Kg of 0.5% levobupivacaine plus isotonic
perineural tramadol, added to the local anesthet-
sodium chloride (0.03 mL/kg) and the i.m. tra-
ic solution, in prolonging postoperative analge-
sia in patients undergoing shoulder arthroscopy
Immediately after the block, all patients also
for rotator cuff tear after middle interscalene received an i.m injection of the study solution
according to the study randomization (either
1.5mg/Kg of 5% tramadol or 0.03ml/Kg of iso-
Materials and methods
35-mm long Teflon-coated needle (Locoplex;
mittee and after written informed consent was Vygon, S.A., Ecouen, France) connected to the
signed, 120 patients (ASA I-II), older than 18 negative lead of the nerve stimulator (Plexival;
years, scheduled for arthroscopic surgery for ro-
Medival, Padova, Italy). The stimulating cur-
rent was initial y set at 0.5 mA, the stimulus
Patients with previous history or clinical frequency at 2 Hz, and impulse duration at 100
evidence of central or peripheral neurological mil iseconds. After local anesthetic infiltration,
disease, coagulopathy or anticoagulant/antiag-
the needle was inserted 2 mm lateral to the sub-
gregant therapy not properly suspended preop-
clavian artery pulse, fol owing a straight line,
eratively, controlateral recurrent and/or phrenic which from the midpoint of the clavicle was the
nerve paresis and those unable to cooperate were lateral tangent of the subclavian artery pulse,
excluded. Patients receiving clonidine, opioids, but lying deeper on the transverse plane of C7
or beta-blockers, and patients with a known spinous process. If no twitch was elicited, small
allergy to any of the study drugs were also ex-
adjustments were made in an anterior or poste-
rior direction until a twitch of the deltoid, bi-
Standardized monitoring was applied (EKG ceps, or triceps muscle was obtained. The stimu-
lead II, blood pressure cuff and pulse oximetry) lating current was progressively decreased to 0.2
and i.v. access secured in all patients. All patients mA. The entire volume was slowly injected un-
were sedated with midazolam 0.02 mg/kg and der intermittent aspiration with a single injec-
haloperidol 2 mg i.v. before performing MIB. All tion technique after ensuring that the twitches
No additional reproduction is author.
subjects underwent a middle interscalene block ceased immediately with injection of 1ml of the
(MIB) as previously described with 0.4 mL/kg anesthetic solution.
of 0.5% levobupivacaine plus the study solution
Sensory blockade of the circumflex, muscolo-
according to the study randomization (either 1.5 cutaneous and radial cutaneous nerves of the
mg/kg of 5% tramadol or 0.03 mL/Kg of iso-
arm were evaluated every 5 minutes until the
tonic sodium chloride).4 After a computerized onset of sensory and motor blockade. Sensory
randomization, all patients were allocated into 1 blockade was tested with the pinprick test in the
territory of distribution of each nerve and de-
1) group placebo (Group P) received the an-
fined as sensory block = no sensation to pinprick
esthetic mixture containing 0.4 mL/kg of 0.5% test or partial sensation to pressure versus no sen-
levobupivacaine plus isotonic sodium chloride sory block = complete sensation to pinprick test,
COPYRIGHT 2012 EDIZIONI MINERVA MEDICA
TRAMADOL AND 0.5% LEVOBUPIVACAINE FOR SINGLE-SHOT INTERSCALENE BLOCK
Table I.—Demographic and anthropometric data (mean±SD).
while motor block was evaluated asking the pa-
tient to raise the arm (circumflex nerve), to ab-
The 3 groups were compared using the Mann-
duct/adduct the thumb (radial/ulnar nerve), to
Whitney U-test for quantitative variables and χ2
oppose the thumb (median nerve) and to flex the tests for qualitative variables. For comparison of
forearm on the arm (musculocutaneous nerve).
parametric data three-way analysis of variance
The anesthesia onset time was defined as the
was applied and for non-parametric data Kruskal-
interval between the end of the injection and
Wal is analysis was fol owed by a Mann-Whitney
the achievement of surgical anesthesia, defined U
-test for three groups. Duration of analgesia
as complete sensory and motor blocks as above was compared by long-rank test. A Pvalue <0.05
described. The incidence of Horner’s syndrome
was considered significant. Data were expressed
If necessary, intraoperative analgesia was sup-
plemented with incremental boluses of fentanyl
i.v. from 50 mcg to a maximum dose of 100
mcg. In case a patient needed more than 100
mcg of fentanyl to complete surgery, the MIB
There was no statistical difference in anthropo-
was evaluated as failed block. If fentanyl sup-
metric data between the three groups (Table I).
plementation was not sufficient to complete sur-
gery, general anesthesia (GA) was administered Horner’s syndrome after MIB, without signifi-
with propofol i.v. infusion and laryngeal mask cant differences among groups. Intraoperatively,
airway. Intraoperatively, heart rate, systolic and heart rate, systolic and diastolic arterial pressure,
diastolic arterial pressure, pulse oximetry and pulse oximetry and respiratory rate remained
stable. No significant differences in the same pa-
In the postoperative period a blinded observer rameters were noted among groups.
collected the Visual Analogue Score (VAS) for
The onset times were not statistically different
pain at rest and nausea/vomiting episodes every in the three groups (Table II).
2 hours. Duration of analgesia was defined as
Intraoperative fentanyl consumptions were
the time elapsed between drug injection and the comparable among the three groups: the mean
first administration of 1g of i.v. acetaminophen fentanyl consumption in Group P was 90.9±20.2
postoperatively, occurring with a VAS > 3. We mcg, in Group TPN was 95.4±15.0 mcg, in
also determined the VAS whenever a patient re-
Group TIM was 96.4±13.3 mcg (P>0.05).
No additional reproduction is author.
quested assistance related to pain. Patients were
Also the incidence of block failure was similar
monitored for 24 hours for the presence of com-
in the three groups: 2 patients in Group P, 2 pa-
plications and side effects, including pruritus, tients in Group TPN and 1 patient in group TIM
nausea/vomiting and hypotension. Nausea and/
required GA with propofol infusion and laryn-
or vomiting were treated with levosulpiride 25 geal mask airway to complete surgery (P>0.05).
Mean duration of analgesia postoperatively
The duration of analgesia was the primary was significantly longer in groups TIM and TPN
outcome variable on which sample size estima-
compared to Group P (Table II). Moreover,
tion was based. The sample size of patients was Group TPN showed a longer duration of analge-
calculated to detect a 10% effect of intervention sia postoperatively than Group TIM (Table II).
with a χ risk of 5% and a power of 80%.
Incidence of nausea and vomiting in the post-
COPYRIGHT 2012 EDIZIONI MINERVA MEDICA
TRAMADOL AND 0.5% LEVOBUPIVACAINE FOR SINGLE-SHOT INTERSCALENE BLOCK
Table II.—Comparison of onset time and duration of analgesia between groups.
A: comparison between Group P and Group TPN; B: comparison between Group P and Group TIM; C: comparison between Group TPN and Group TIM
operative period did not show any significant of tramadol 100 mg to mepivacaine 1% for axil-
difference among the three groups: we regis-
lary plexus block prolonged sensory and motor
tered 2 cases in Group P (5%), 4 cases in Group block compared with mepivacaine alone or axil-
TIM (10%) and 3 cases in Group TPN (7.5%) lary block with tramadol 100 mg i.v.18 Robaux
et al. demonstrated that tramadol extends the
duration and improves the quality of postopera-
tive analgesia in a dose-dependent fashion when
Discussion
combined with mepivacaine 1.5% for brachial
Our study shows that tramadol added to sin-
plexus block.19 The incidence of adverse effects
gle-shot interscalene block, either perineurally also increased with larger doses, but the side ef-
or intramuscular, provides a longer duration fect profile remained acceptable up to 200 mg
of postoperative analgesia when compared to tramadol in their study. However, a systemic
interscalene block performed with 0.5% lev-
tramadol group was not included in their study.
obupivacaine alone. Moreover, when tramadol is More recently, Kaabachi et al. reported that 200
added as an adjuvant to single-shot interscalene mg tramadol prolong block duration and post-
block, it provides a longer relief from postopera-
operative analgesia when axillary block is per-
tive pain than systemic tramadol, prolonging the formed with 1.5% lidocaine and epinephrine
time-to-first-analgesic-request in patients under-
1/200000.20 However, a high dose of tramadol
gone arthroscopic repair of rotator cuff tear.
was also associated with a delayed onset of an-
Tramadol is known as an atypical analgesic esthesia, maybe related to the dilutional effect
with some local anesthetic actions as wel as of tramadol added to the local anesthetic solu-
central opioidergic, noradrenergic, and seroton-
tion.20 Also Antonucci et al. evaluated the use
ergic actions.1, 2 Many mechanisms have been of tramadol as adiuvant in carpal tunnel release
advocated to explain tramadol’s peripheral ac-
performed under axillary plexus block with
tion on pain, including tramadol’s agonism at 0.75% ropivacaine 20 mL.21 Tramadol proved to
peripheral a2 receptors (similarly to clonidine), provide a significative reduction of onset time,
its agonism in the dorsal lamine of the spinal a prolongation of anesthesia and analgesia with
cord through serotonin subtype 3 (5-HT3) re-
lower incidence of side effects than clonidine
ceptors and its postulated local anesthetic prop-
No additional reproduction is author.
erties possibly by blocking K+ channels.16 Re-
Other studies failed to demonstrate the effi-
cently, Wang et al. have also demonstrated its cacy of tramadol as an adjunct to local anesthetic
efficacy in antagonizing glutamate N-methyl-
for brachial plexus block. In Kesimci et al., 42
D-aspartic acid (NMDA) receptors that are mL local anesthetic solution consisting of 0.75%
known to be involved in the pathophysiology ropivacaine together with 100 mg tramadol was
used for patients undergoing hand and forearm
Although these promising results, direct com-
surgery and axillary brachial plexus blockade.22
parison of studies involving tramadol for region-
No effect of tramadol on block duration, onset
al anesthesia is difficult, as very few studies have times and analgesia duration was seen. In a study
by Broch and Breucking, brachial plexus block-
Kapral et al. demonstrated that the addition ade was performed by adding 1.5 mg/kg trama-
COPYRIGHT 2012 EDIZIONI MINERVA MEDICA
TRAMADOL AND 0.5% LEVOBUPIVACAINE FOR SINGLE-SHOT INTERSCALENE BLOCK
dol or 1.5 mg/kg clonidine or placebo to 40 mL adverse events were reported in our study after
of 1.5% prilocaine: a significant prolongation of the perineural administration of 1.5 mg/Kg of
sensory and motor block was demonstrated only tramadol.
in the clonidine group, whether tramadol failed
to prove its postulated efficacy.23 Also Sarsu et Conclusions al. showed that adding 100 mg of tramadol to
the combination of levobupivacaine and lido-
In conclusion, when added to single-shot
caine during axillary (40 mL of local anesthetic middle interscalene block performed with 0.5%
solution) brachial plexus block was not effective
levobupivacaine, tramadol extends the duration
in shortening the block onset, lengthening the of postoperative analgesia without significant
block in axillary brachial plexus blockade in pa-
tients undergoing hand and forearm surgery.24
These contrasting results from previous litera-
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Received on March 10, 2011 - Accepted for publication on September 5, 2011.
Corresponding author: D. Ghisi, MD, Department of Anesthesia and Pain Therapy, Istituti Ospitalieri di Cremona, Viale Concordia 1,
26100 Cremona, Italy. E-mail: ghisidan@hotmail.com
This article is freely available at www.minervamedica.it
No additional reproduction is author.
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