The Efficacy of the Non-Opioid Analgesics Parecoxib,

Paracetamol and Metamizol for Postoperative Pain Relief

After Lumbar Microdiscectomy
Ulrich Grundmann, MD* In this prospective, double-blind, randomized, placebo-controlled study we com-
pared the efficacy of three IV non-opioid analgesics for postoperative pain relief
Clemens Wörnle, MD* after lumbar microdiscectomy. Eighty healthy patients were randomly divided into
4 treatment groups (n ⫽ 20 each) to receive either parecoxib 40 mg, paracetamol 1 g,
metamizol 1 g, or placebo IV 45 min before the end of surgery. In the postanesthesia
Andreas Biedler, MD* care unit (PACU) patients were treated using patient-controlled analgesia (PCA)
with piritramide. In the metamizol group the pain score at arrival in the PACU was
Sascha Kreuer, MD* significantly lower compared with the paracetamol, parecoxib, and placebo groups.
In addition, in the metamizol group significantly fewer patients required additional
Marc Wrobel, MD* PCA compared with the other groups studied. However, in those patients who
required additional pain therapy in the four treatment groups, there was no
Wolfram Wilhelm, MD† significant difference in time to first request for piritramide and cumulative
consumption of piritramide as assessed by the PCA data in the PACU. The
incidence of adverse side effects was infrequent in all groups. These results suggest
that in patients undergoing lumbar microdiscectomy, metamizol is superior to
parecoxib, paracetamol, and placebo for immediate postoperative pain relief with
minimal side effects.
(Anesth Analg 2006;103:217–22)

A lthough multiple modalities, including tissue in-

filtration with corticosteroids and local anesthetics (1),
epidural administration of anesthetics (2), or cooling
methods (3), have been advocated to reduce postop-
erative pain after lumbar disk surgery, systemic ad-
ministration of analgesics is still the most widely used
method. Besides opioids, nonsteroidal antiinflamma-
tory drugs (NSAIDs) play an important role in this
clinical setting. Their analgesic effect is based on a
diminished prostaglandin synthesis by inhibition of
the cyclooxygenase (COX) enzyme in the arachidonic
acid metabolism. The discovery of at least two COX
isoforms led to the development of selective COX-2-
inhibitors (coxibs) that were thought to have an im-
proved risk-benefit ratio compared with traditional
NSAIDs. Two studies have shown that oral adminis-
tration of coxibs can result in pain relief after disk
surgery (4,5). However, parecoxib, the only parenter-
ally administered coxib, has not been investigated
From the *Department of Anesthesiology and Intensive Care
Medicine, University of Saarland, Homburg/Saar, Germany; and
†Department of Anesthesiology and Intensive Care Medicine, St.-
Marien-Hospital Lünen, Lünen, Germany.
Accepted for publication March 14, 2006.
Address correspondence and reprint requests to Ulrich Grund-
mann, MD, Department of Anesthesiology and Intensive Care
Medicine, University of Saarland, D-66421 Homburg/Saar, Ger-
many. Address e-mail to grundmann.ulrich@web.de.
Copyright © 2006 International Anesthesia Research Society
DOI: 10.1213/01.ane.0000221438.08990.06
under these conditions and, even more important, a
comparison with other non-opioid analgesics is still
missing. We therefore designed the present study to
assess the analgesic effects of parecoxib and two other
injectable non-opioids, paracetamol and metamizol,
for postoperative pain relief in patients undergoing
lumbar microdiscectomy.
METHODS
With approval of the local Ethics Committee and
written informed consent 80 patients of either sex
scheduled for single level, unilateral microsurgical
lumbar discectomy were enrolled in this prospective,
randomized, double-blind, placebo-controlled study.
Inclusion criteria were the following: patients between
the ages of 18 and 75 yr and ASA physical status I-II.
Patients with a history of significant cardiac, pulmo-
nary, hepatic, or renal disease, body mass index ⬍18.5
or ⬎35, chronic drug or alcohol abuse, and contrain-
dications or previous adverse reaction to any of the
drugs used in the study were excluded. Not included
were females with a positive pregnancy test and
patients unable to cooperate.
After informed consent, patients were assigned
randomly to one of four study groups. Randomization
was performed using a sealed opaque envelope with
a computer-generated block random allocation
(http://www.randomizer.org/). The four study
groups were 1) parecoxib 40 mg, 2) paracetamol 1 g, 3)
metamizol 1 g, and 4) placebo. The patients received

Vol. 103, No. 1, July 2006 217

the drugs dissolved in 100 mL normal saline via IV
infusion over 15 min. Patients of the placebo group
received 100 mL of normal saline as a control. The
study solutions were prepared by one of the research-
ers (WW) who was not involved in the intraoperative
and postoperative treatment of these patients,
whereas postoperative data were collected by another
anesthesiologist (CW) who was blinded as to the
drugs used. The group assignment code was retained
until the conclusion of the study. To ensure patient
safety, however, a sealed opaque envelope containing
the name of the drug was kept with the patient in the
operating room (OR), the postanesthesia care unit
(PACU), and on the ward to permit immediate un-
masking if necessary.
All patients had fasted overnight and were pre-
medicated with 10 mg diazepam orally both the night
before surgery and 90 min before induction of anes-
thesia. On arrival in the OR an 18-gauge cannula was
inserted into a forearm vein and standard monitors
were applied. Heart rate, oxygen saturation, and the
bispectral index of the electroencephalogram (BIS
A-2000 monitor, software version XP; Aspect Medical
Systems Inc., Newton, MA) were monitored continu-
ously and noninvasive arterial blood pressure was
recorded every 5 min throughout anesthesia. Before
induction all patients received 5 mL/kg of IV fluid
over 20 min. Oxygen was administered via an anes-
thetic breathing circuit and facemask. After 5 min of
administration of oxygen anesthesia was induced in
all patients with 2 mg/kg propofol and 2 ␮g/kg
fentanyl followed by 0.5 mg/kg atracurium to facili-
tate tracheal intubation and to maintain neuromuscu-
lar blockade, monitored by the train-of-four stimula-
tion method using a peripheral nerve stimulator. After
tracheal intubation, patients received a total IV anes-
thesia with 0.25 ␮g 䡠 kg⫺1 䡠 min⫺1 remifentanil and
3– 6 mg 䡠 kg⫺1 䡠 h⫺1 propofol. The infusion rate of
propofol was adjusted to maintain the Bispectral index
values between 40 and 45. The lungs were ventilated
with an air/oxygen mixture (Fio2 0.35– 0.45) at a flow
rate of 1 L/min in a semiclosed system (Cato; Dräger
AG, Lübeck, Germany). The inspired oxygen and
end-tidal concentrations of carbon dioxide (CO2) were
measured continuously at the proximal end of the
endotracheal tube using a calibrated infrared gas
analyzer (Dräger pm 8050, Dräger). Ventilation was
adjusted to maintain normocapnia as measured by
end-tidal CO2. Forty-five minutes before the expected
end of surgery the non-opioid analgesics were infused
over a period of 15 min. At the completion of surgery
the administration of maintenance anesthetics was
discontinued without tapering. The lungs of each
patient were ventilated with 100% oxygen at a flow
rate of 5 L/min. Spontaneous recovery of neuromus-
cular function was confirmed by train-of-four moni-
toring. The trachea was extubated when adequate
spontaneous ventilation (tidal volume ⬎5 mL/kg) and
response to verbal commands were established. The
218 Non-Opioid Analgesics and Pain Relief
last surgical stitch was defined as the end of surgery.
During emergence from anesthesia the following recov-
ery times were recorded: end of surgery until spontane-
ous opening of eyes, tracheal extubation, stating name
and date of birth.
Thereafter, the patients were directly transferred
to the PACU, where further clinical observations
were done by an independent, blinded observer
who was unaware of the administered study drugs.
During a 120-min observation period hemodynamic
variables were recorded. The severity of postopera-
tive side effects (nausea, vomiting, shivering, and
pruritus) was quantified using different scales. The
scale for nausea, pruritus, and shivering was 0 ⫽
none, 1 ⫽ mild, 2 ⫽ severe. The scale for postopera-
tive vomiting was 0 ⫽ none, 1 ⫽ 1 or 2 episodes, and
3 ⫽ more than 2 episodes. In the PACU patients
were asked every 10 min to quantify their pain
experience at rest on a visual analog scale (VAS)
between 0 and 100, with 0 representing no pain and
100 the worst imaginable pain. Postoperative pain
was treated by self-administration of small doses of
IV piritramide using a patient-controlled analgesia
(PCA) pump (Injectomat®, PCA-PACOM; Fresenius
AG, Germany). The PCA was programmed to ad-
minister a bolus dose of 3 mg piritramide on patient
demand, with a 2 h limit of 30 mg and a lockout
interval of 5 min. The cumulative piritramide con-
sumption at discharge from the PACU and side
effects were recorded. During the preoperative as-
sessment patients were instructed how to use the
VAS and the PCA pump. Furthermore any intraop-
erative and postoperative adverse events (e.g., alter-
ations of heart rate and arterial blood pressure) after
the administration of the study drugs were assessed
and recorded.
Data were processed in Microsoft® Excel 2002,
SigmaStat® 3.0.1 and SigmaPlot® 8.02 (SPSS Science
Software GmbH, Erkrath, Germany). To calculate the
number of patients needed for the study, we evaluated
the anesthetic and postoperative charts of patients in
our hospital that had been operated on before the start
of this study. Based on the assumptions that 1) 1 g
metamizol would produce a 55% decrease in the VAS
score (sd, 14) and 2) a type I error ␣ ⫽ 0.05 and Type
II error ␤ ⫽ 0.2, an a priori power analysis suggested a
sample size of 18 patients for each group. To compen-
sate for dropouts, e.g., withdrawal of consent or
technical problems with the PCA pump, 20 patients
per group were included. Mean values and sd were
calculated for all variables. Differences among the
groups were calculated by one-way analysis of vari-
ance followed by pairwise comparisons using a post
hoc Student-Newman-Keuls-test. Categorical data
were analyzed using ␹2 or Fisher’s exact test as
appropriate. Differences were judged significant at
P ⬍ 0.05.
ANESTHESIA & ANALGESIA
Table 1. Patient Characteristics
Parecoxib Paracetamol Metamizol Placebo
(n ⫽ 20) (n ⫽ 20) (n ⫽ 20) (n ⫽ 20)
Age (yr) 44.1 ⫹ 11.3 48.1 ⫹ 14.0 43.6 ⫹ 13.7 48.1 ⫹ 11.4
Height (cm) 174.9 ⫹ 11.0 172.8 ⫹ 6.9 175.4 ⫹ 9.7 170.0 ⫹ 10.1
Weight (kg) 83.4 ⫹ 12.8* 75.9 ⫹ 8.8 80.3 ⫹ 13.8 72.8 ⫹ 11.5
Body mass index (kg/m-2) 27.3 ⫹ 3.4 25.4 ⫹ 2.5 26.0 ⫹ 3.5 25.2 ⫹ 3.6
Gender (male/female) 12/8 11/9 13/7 7/13
ASA physical status (I/II) 5/15 0/20 4/16 0/20
Duration of surgery (min) 89.8 ⫹ 30.7 80.0 ⫹ 31.6 88.1 ⫹ 31.6 90.3 ⫹ 23.8
Data are shown as mean ⫹ SD or number of patients as appropriate.
*P ⬍ 0.05 parecoxib versus placebo.

RESULTS with one episode of vomiting immediately after ar-

Eighty patients were enrolled in the study with 20
patients in each group. In all patients a complete data
set was obtained. Because there was no protocol
violation in any of the patients studied, the data of all
80 patients could be used for statistical analysis.
The four groups were similar with respect to gen-
der, age, height, body mass index, ASA physical
status, and duration of surgery. Despite random as-
signment, patients of the parecoxib group had a
slightly higher body weight than those in the placebo
group (Table 1). None of the study drugs had any
major effects on the hemodynamic variables, and there
were no significant between-group differences. Emer-
gence from anesthesia was comparable for all groups
studied (Table 2). There was no significant difference
in the time required for emergence from anesthesia as
defined by eye opening, time to tracheal extubation,
and orientation time (time at which each patient was
able to state his or her name and date of birth).
Data of the PACU evaluation are presented in Table
3. At arrival in the PACU postoperative VAS pain
scores were significantly lower in the metamizol
group compared with the paracetamol, parecoxib, and
placebo groups. In addition in the metamizol group,
significantly fewer patients required additional PCA
compared with the other groups. However, in patients
requiring additional pain therapy there was no signifi-
cant difference in time to first request for piritramide
and cumulative consumption of piritramide as as-
sessed by the PCA data in the PACU. At discharge
from the PACU 2 h after admission, VAS pain scores
at rest were similar in all groups. Overall, we observed
infrequent nausea and vomiting although the patients
had not received an antiemetic prophylaxis. One pa-
tient in each treatment group suffered from mild
nausea, and there was one patient receiving parecoxib
rival in the PACU. Shivering was rare and mostly mild
in all groups except for placebo, but this difference did
not reach statistical significance. None of the patients
complained of pruritus and no other complications
were observed. The incidence of agranulocytosis was
not addressed in any special way in the study design,
but routine postoperative blood cell counts revealed
no evidence of this adverse effect and all the patients
were discharged from the hospital in good condition.
DISCUSSION
The results of this study demonstrate that met-
amizol provides effective analgesia in the early post-
operative period after lumbar microdiscectomy. Pa-
tients who received a single IV dose of metamizol 1 g
experienced pain relief that was superior to parecoxib
40 mg, paracetamol 1 g, and placebo as assessed by
VAS scores at arrival in the PACU.
Compared with previous studies addressing pain
relief after lumbar disk surgery (4,6) the magnitude of
the VAS scores in patients receiving placebo were
minor in our trial. This low pain intensity might be
explained, in part, by the microsurgical technique
resulting in a small tissue trauma and by successful
removing of herniated nucleus pulposus material
causing radicular symptoms. Because the microsurgi-
cal technique was used in the previous studies as well,
the reason for this difference remains unclear.
Although the introduction of microsurgical tech-
niques has reduced analgesic requirements, postop-
erative pain caused by the operation itself or by the
wound is unavoidable. Opioid analgesics are the
traditional first-line medication in this setting but may
induce unwanted side effects, such as nausea and
vomiting, sedation, and respiratory depression. Sev-
eral studies have shown that non-opioid analgesics

Table 2. Emergence and Orientation Times

Parecoxib Paracetamol Metamizol Placebo
(n ⫽ 20) (n ⫽ 20) (n ⫽ 20) (n ⫽ 20)
Eye opening (min) 7.0 ⫹ 3.7 6.0 ⫹ 2.7 6.0 ⫹ 3.4 7.2 ⫹ 3.8
Extubation (min) 8.7 ⫹ 3.7 7.5 ⫹ 3.2 7.8 ⫹ 2.9 8.9 ⫹ 3.4
Name (min) 9.3 ⫹ 3.7 8.4 ⫹ 3.3 8.5 ⫹ 2.7 9.6 ⫹ 3.2
Date of birth (min) 9.3 ⫹ 3.7 8.4 ⫹ 3.3 8.5 ⫹ 2.7 9.6 ⫹ 3.2
Data are shown as mean ⫹ SD. No significant differences were observed among groups.

Vol. 103, No. 1, July 2006 © 2006 International Anesthesia Research Society 219
Table 3. Postanesthesia Care Unit Evaluation (2-h Observation Period)
Parecoxib
(n ⫽ 20)
VAS at arrival 32.5 ⫹ 21.4
VAS at discharge 13.3 ⫹ 10.1
Patients requiring additional pain therapy (n) 17
Time to first postoperative analgesic (min) 19.5 ⫹ 14.1
Cumulative piritramide doses after 1 h 8.5 ⫹ 3.4
Cumulative piritramide doses after 2 h 10.9 ⫹ 5.7
HR at arrival (bpm) 74.6 ⫹ 13.4
MAP at arrival (mm Hg) 94.3 ⫹ 27.3
Nausea (n) 1 1
Vomiting (n) 1 0
Shivering (n) 2 1
Pruritus (n) 0 0
Data are shown as mean ⫹ SD or number of patients as appropriate. VAS ⫽ visual analogue scale; PACU ⫽ postanesthesia care unit; HR ⫽ heart rate; MAP ⫽ mean arterial blood pressure.
*P ⬍ 0.05 versus parecoxib, paracetamol, placebo.
provide effective pain relief in patients with acute
postoperative pain after lumbar disk surgery, either as
a substitute for or as an adjunct to opioid analgesia
(4,7,8). However, this is the first prospective, random-
ized, double-blind, placebo-controlled study that com-
pares IV administered parecoxib, paracetamol, and
metamizol for pain relief in the early postoperative
period after lumbar disk surgery.
In the present study the injectable form of analge-
sics was chosen, as in the perioperative setting many
patients cannot tolerate oral medication or may have
variable gastrointestinal absorptive function. Pare-
coxib, the only parenterally administered coxib avail-
able, is a prodrug that is converted in the liver to its
active metabolite valdecoxib (9). In the paracetamol
group we administered a new, ready-to-use IV solu-
tion of paracetamol (Perfalgan™ 10 mg/mL; Bristol-
Myers Squibb GmbH, München, Germany). Results of
a bioequivalence study comparing this new paraceta-
mol solution and the IV prodrug propacetamol indi-
cate that 1 g of paracetamol administered as Perfal-
gan™ is equivalent to 2 g of propacetamol with minor
application side effects (10). The third analgesic used
in this study, metamizol, a pyrazolone derivate, pro-
vides additional antipyretic, antispasmodic, and anti-
inflammatory effects. It is a very popular non-opioid
analgesic in Germany, Spain, and South America
whereas in other countries it has been banned because
of its disputed association with potentially life-
threatening agranulocytosis (11).
Although there is no doubt that metamizol may
cause agranulocytosis, reports on the risk of
metamizol-associated agranulocytosis suggest widely
varying estimates. Although Hedenmalm and Spigset
(12) reported an incidence of 1 case per 1431 prescrip-
tions in Sweden, Ibanez et al. (13) concluded that in
Spain the absolute risk of metamizol-associated
agranulocytosis at usual doses and for short treatment
periods is very small, with a calculated incidence of
0.56 cases per million inhabitants per year. Thus,
considering these data, uncertainty remains and the
only way to clarify the real incidence would be to do
220 Non-Opioid Analgesics and Pain Relief
Paracetamol Metamizol Placebo
(n ⫽ 20) (n ⫽ 20) (n ⫽ 20)
36.4 ⫹ 19.5 14.2 ⫹ 14.7* 29.9 ⫹ 20.1
20.9 ⫹ 14.7 9.4 ⫹ 9.8 11.4 ⫹ 14.6
19 11* 18
17.1 ⫹ 13.8 19.3 ⫹ 22.3 10.8 ⫹ 10.2
9.5 ⫹ 4.2 9.3 ⫹ 4.1 8.2 ⫹ 3.1
13.7 ⫹ 4.8 10.9 ⫹ 6.2 10.7 ⫹ 4.4
76.1 ⫹ 13.1 68.9 ⫹ 11.9 80.6 ⫹ 15.0
90.0 ⫹ 9.2 96.9 ⫹ 18.0 91.8 ⫹ 12.3
1 1
0 0
2 6
0 0
a large prospective study in countries that are
routine users of metamizol. Until then, patients
should probably be monitored for blood dyscrasias,
especially if long-term use is intended. If agranulo-
cytosis occurs, therapy with broad-spectrum antibi-
otics and hematopoietic growth factors will reduce
the mortality in those patients. However, in the
discussion of metamizol-induced agranulocytosis
the risk of this side effect should be considered in
comparison with other potentially life-threatening
adverse effects of alternative analgesics. Although
NSAIDs account for a substantial risk of gastroin-
testinal bleeding, renal failure, or severe skin reac-
tion, metamizol is relatively safe concerning these
side effects. Andrade et al. (14), evaluating epide-
miological studies of non-narcotic analgesic safety
published from 1970 to 1995, estimated the excess
mortality as a result of agranulocytosis, aplastic
anemia, anaphylaxis, and serious upper gastrointes-
tinal complications as 25/100 million for metamizol,
20/100 million for paracetamol, 185/100 million for
aspirin, and 592/100 million for diclofenac; most of
these complications were related to gastrointestinal
side effects. The authors concluded that a relative
risk estimate of 300 or more for the association of
metamizol with agranulocytosis would have been
necessary for the excess mortality of metamizol to
be comparable to that of aspirin or diclofenac.
Although all the drugs studied belong to the group
of non-opioid analgesics, they act by different mecha-
nisms. The analgesic action of parecoxib results from
the inhibition of the COX-2 isoenzyme that plays an
important role in the synthesis of prostaglandin E2 in
the traumatized area by increasing the threshold of
activation of the nociceptors. In contrast, despite the
long use of metamizol and paracetamol their mode of
action is still not fully understood. Generally consid-
ered as belonging to the NSAIDs there is only a weak
inhibition of prostaglandin synthesis and a lack of
other typical actions of NSAIDs, such as antiplatelet
activity and gastrotoxicity, suggesting a distinct mode
ANESTHESIA & ANALGESIA
of action. A third COX isoenzyme, COX 3, was iden-
tified, and the inhibition of this isoform could repre-
sent a primary central mechanism by which these
drugs decrease pain (15).
As information indicating equipotent doses of the
non-opioid analgesics are still missing for lumbar disk
surgery, we decided to choose the maximum doses
recommended by the manufacturers for initial IV use
in adults, i.e., parecoxib 40 mg, paracetamol 1 g, and
metamizol 1 g, respectively. Thus, even if it is as-
sumed that in the present study the dosing of parac-
etamol and parecoxib was too small for adequate pain
relief when compared to metamizol, simply increasing
the dose of paracetamol or parecoxib cannot be
recommended.
A comparison of our results concerning the analge-
sic efficacy with the results of previous studies is
difficult because of different application times, routes,
and dosages used for the respective non-opioids. In a
placebo-controlled study designed to evaluate the
concept of balanced analgesia after vertebral disk
surgery Fletcher et al. (16) compared IV propacetamol
and ketoprofen given alone or in combination postop-
eratively. Similar to the present study with paraceta-
mol, pain scores and cumulative morphine consump-
tion did not differ in the group receiving
propacetamol compared with placebo. Hans et al. (17)
also failed to demonstrate an analgesic efficacy of
propacetamol hydrochloride in the early postopera-
tive period after lumbar disk surgery when adminis-
tered at the end of the procedure. Because data for
parecoxib and metamizol are missing for lumbar spine
surgery, we have to consider the results of trials in
different types of surgery. Avellaneda et al. (18), using
a dosage of 2 g metamizol and a dosage of 1 g
propacetamol, demonstrated comparable analgesic ef-
fects of metamizol and propacetamol after heart sur-
gery. Consistent with the results of our study, met-
amizol provided better pain relief than paracetamol
after oral administration of 1 g every 6 h of the
respective analgesic after ambulatory hand surgery
(19). The effect of parecoxib on postoperative pain
relief was studied in minor and major surgical proce-
dures. In contrast to our findings, parecoxib usually
demonstrated analgesic efficacy superior to placebo
and similar to ketorolac (20 –22).
There are possible concerns regarding the side
effects of the analgesics used in this study. Both
metamizol and paracetamol are reported to cause
hypotension that may be poorly tolerated by critically
ill patients (18,23) or by patients in a prone position,
which is usually used for lumbar spine surgery. In
contrast, based on the results obtained in the present
study, the three study drugs were well tolerated in
this relatively healthy population with no difference
from placebo. Of note, the analgesics showed no
adverse hemodynamic effects, probably because they
were continuously infused over 15 minutes rather
than injected as a bolus. In the present study there
Vol. 103, No. 1, July 2006
were no adverse cardiovascular events such as myo-
cardial infarction, thromboembolism, or deep vein
thrombosis. It must be emphasized that none of the
studies evaluating COX-2-inhibitors for postoperative
analgesia reported an increased risk of cardiovascular
events, except for two patient studies after coronary
artery bypass graft surgery comparing IV
parecoxib/oral valdecoxib versus placebo (24,25).
Based on these data, valdecoxib and parecoxib are
considered to be contraindicated in patients undergo-
ing coronary artery bypass graft surgery. The precise
mechanism responsible for the increased cardiovascu-
lar risk is unknown, but there is a mechanistic hypoth-
esis that COX-2 inhibitors might increase the risk of
thromboembolic events because of the inhibition of
prostacyclin in the vascular endothelium without the
concomitant inhibition of platelet thromboxane A2
generation, causing an imbalance of procoagulatory
and anticoagulatory factors. The relevance of the
increased cardiovascular risk caused by coxibs after
long-term treatment for patients on short-term post-
operative pain therapy is unclear. Nevertheless, the
German Drug Safety Board (“Arzneimittelkommis-
sion der Deutschen Ärzteschaft”) recommends not
using coxibs in the perioperative setting (26); however,
this recommendation was published several weeks
after the present study had been finished. It is note-
worthy that in postmarketing experience serious skin
reactions have been described with parecoxib and
valdecoxib, and the reported rate appears to be more
than with other COX-2-inhibitors. Obviously patients
appear at highest risk for these events early in the
course of therapy and also patients without a history
of sulfonamide allergy are at risk. Based on these new
data, the Food and Drug Administration and the
European Agency for the Evaluation of Medicinal
Products now recommend discontinuing the use of
parecoxib/valdecoxib at the first appearance of skin
rash, mucosal lesions, or any other signs of
hypersensitivity.
In this study piritramide, a synthetic opioid struc-
turally related to meperidine, was chosen for PCA. Its
relative analgesic potency compared with morphine is
approximately 0.7. Because piritramide is distributed
extensively and eliminated slowly, the pharmacoki-
netic profile of the drug allows for intermittent bolus
administration even when relatively constant effect
compartment concentrations are desirable, e.g., for
PCA (27).
Despite avoiding antiemetic prophylaxis, the inci-
dence of postoperative nausea and vomiting in all
groups was less than previously reported (6). Besides
patient-related factors, the use of total IV anesthesia
with propofol may have contributed to these results,
as previous studies indicated that propofol appears to
have an inherent antiemetic effect (28,29).
In terms of pharmacoeconomics, acquisition costs
at our hospital are 0.18€ for 1 g of metamizol, 6.86€ for
40 mg of parecoxib, and 2.12€ for 1 g of paracetamol.
© 2006 International Anesthesia Research Society 221
Thus, postoperative pain treatment with metamizol is
not only the most effective but also the least expensive
method. This cost-saving effect will be much more
pronounced if the analgesics are continued to the
maximal dose for daily use of metamizol 5 g, pare-
coxib 80 mg, and paracetamol 4 g respectively.
The study also has certain limitations. The lack of
significant differences among the analgesic effects of
paracetamol, parecoxib, and placebo must be inter-
preted with some caution, as they could be real or
could be related to the methodology of the study
evaluating patients undergoing lumbar microdiscec-
tomy, which might have lacked the appropriate assay
upside sensitivity related to the moderate level of pain
(VAS ⬍ 30), probably as a result of the microsurgical
technique and successful removing of herniated
nucleus pulposus material. In addition, pain intensity
was evaluated only at rest; thus it remains unclear if
there would be identical results for movement-related
pain relief. Consequently, further studies in more
painful surgical models are needed for clarification.
Furthermore, the limited period of evaluation (2 hours
in the PACU) was not long enough to give adequate
long-term outcome information. However, with re-
spect to the investigated drugs and side effects, our
data sufficiently demonstrate that non-opioid treat-
ment is not associated with an increase of adverse
effects compared with placebo.
In conclusion, in patients undergoing lumbar mi-
crodiscectomy, the IV administration of a single dose
of metamizol 1 g provides significantly better pain
control in the early postoperative period compared
with other non-opioids without increasing adverse
side effects. Parecoxib and paracetamol failed to im-
prove postoperative pain relief when compared with
placebo, but this lack of differences must be inter-
preted with some caution because of the low VAS
scores observed in this study.
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ANESTHESIA & ANALGESIA