REPORTS OF ORIGINAL INVESTIGATIONS

The addition of epidural local anesthetic to systemic multimodalanalgesia following lumbar spinal fusion: a randomized controlledtrial

L’ajout d’un anesthesique local en peridural a une analgesiemultimodale systemique apres une fusion lombaire: une etuderandomisee controlee

Stephen Choi, MD • Y. Raja Rampersaud, MD • Vincent W. S. Chan, MD •

Oma Persaud, MSc • Arkadiy Koshkin, MD • Paul Tumber, MD •

Richard Brull, MD

Received: 16 September 2013 / Accepted: 15 January 2014

� Canadian Anesthesiologists’ Society 2014

Abstract

Purpose This randomized trial aimed to evaluate the effects

of adding continuous epidural analgesia with a bupivacaine

and hydromorphone solution to systemic multimodal

analgesia following one- or two-level lumbar spinal fusion.

Methods Thirty-nine patients undergoing lumbar spinal

fusion, stratified for sex and one- or two-level fusion, were

randomized to receive a continuous postoperative epidural

infusion of either 0.1% bupivacaine with 15 lg�mL-1

hydromorphone (LA group) or 0.9% saline (NS group) at

6 mL�hr-1 for 48 hr through an epidural catheter placed

intraoperatively. All patients received a standardized

postoperative multimodal analgesia regimen. Patients,

healthcare providers, and research staff were blinded.

The primary outcome measure was cumulative opioid

consumption (oral morphine equivalent) during the first

48 hr postoperatively.

Results The mean (SD) cumulative opioid consumption

48 hours postoperatively was 249.3 (143.3) mg in the NS

group and 184.7 (208.1) mg in the LA group (mean difference

64.6 mg; 95% confidence interval -54.3 to 183.5; P = 0.27).

There were no adverse events in either group.

Conclusion Continuous epidural infusion combined with

systemic multimodal analgesia resulted in a mean

reduction in 48-hr cumulative opioid consumption of

64.6 mg (95% confidence interval -54.3 to 183.5)

following one- or two-level lumbar spinal fusion. This

estimate of effect is imprecise, and the routine use of

continuous epidural analgesia in this surgical population is

not yet warranted. This trial was registered at www.

clinicaltrials.gov: NCT00644111.

Resume

Objectif Cette etude randomisee avait pour but

d’evaluer les effets de l’adjonction d’une analgesie

peridurale continue avec une solution de bupivacaıne et

d’hydromorphone a une analgesie multimodale systemique

apres une fusion lombaire a un ou deux niveaux.

Methode Trente-neuf patients subissant une fusion

lombaire, stratifies selon leur sexe et leur fusion lombaire

(a un ou deux niveaux), ont ete randomises a recevoir une

perfusion peridurale postoperatoire continue avec soit

0,1 % de bupivacaıne et 15 lg�mL-1 d’hydromorphone

Author contributions Stephen Choi, Y. Raja Rampersaud, VincentW.S. Chan, Paul Tumber, and Richard Brull helped design the study.Stephen Choi, Y. Raja Rampersaud, Vincent W.S. Chan, OmaPersaud, Arkadiy Koshkin, and Richard Brull helped conduct thestudy. Stephen Choi, Y. Raja Rampersaud, Oma Persaud, andArkadiy Koshkin helped analyze the data. Stephen Choi, Y. RajaRampersaud, Vincent W.S. Chan, Paul Tumber, and Richard Brullhelped write the manuscript. Richard Brull is responsible forarchiving the study files.

S. Choi, MD

Department of Anesthesia, Sunnybrook Health Sciences Centre,

Toronto, ON, Canada

Y. R. Rampersaud, MD � O. Persaud, MSc

Division of Orthopedic Surgery, Toronto Western Hospital,

University Health Network, Toronto, ON, Canada

V. W. S. Chan, MD � A. Koshkin, MD � P. Tumber, MD �R. Brull, MD (&)

Department of Anesthesia and Pain Management, Toronto

Western Hospital, 399 Bathurst Street, Toronto, ON M5T 2S8,

Canada

e-mail: richard.brull@uhn.ca

123

Can J Anesth/J Can Anesth

DOI 10.1007/s12630-014-0115-z

(groupe LA) ou 0,9 % de normal salin (groupe NS) a

6 mL�h-1 via un catheter peridural place en periode

peroperatoire. Tous les patients ont recu un regime

d’analgesie multimodale postoperatoire standardise. Les

patients, les professionnels de la sante et le personnel de

recherche etaient tous en aveugle. La principale mesure

d’evaluation etait la consommation cumulative d’opioıdes

(equivalent morphine orale) pendant les premieres 48 h

postoperatoires.

Resultats La consommation cumulee moyenne (ET)

d’opioıdes a 48 h postoperatoires etait de 249,3

(143,3) mg dans le groupe NS et de 184,7 (208,1) mg

dans le groupe LA (difference moyenne 64,6 mg; intervalle

de confiance 95 % -54,3 a 183,5; P = 0,27). Aucun effet

secondaire nefaste n’a ete observe dans les deux groupes.

Conclusion La combinaison d’une perfusion peridurale

continue a une analgesie multimodale systemique a entraıne

une reduction moyenne de la consommation cumulative

d’opioıdes pendant les 48 h suivant l’operation de 64,6 mg

(intervalle de confiance 95 % -54,3 a 183,5) suivant une

fusion lombaire a un ou deux niveaux. L’estimation de l’effet

est imprecise, et l’utilisation de routine d’une analgesie

peridurale continue chez cette population chirurgicale n’est

pas encore justifiee. Cette etude a ete enregistree au www.

clinicaltrials.gov: NCT00644111.

The optimal analgesic regimen for patients undergoing

lumbar decompression and fusion is unclear. A recent

systematic review of the literature was unable to show

superiority of either epidural analgesia or systemic analgesia

after lumbar decompression and fusion.1 When compared

with systemic analgesia, some studies have determined that

epidural analgesia using local anesthetic alone or in

combination with epidural opioids can provide excellent

pain control and reduce opioid consumption following

conventional open spinal surgery.2-6 On the other hand,

other studies have failed to detect any clinically meaningful

advantages of epidural analgesia in similar settings.7-11

Presumably the absence of conclusive evidence stems

from several factors, most notably heterogeneous samples of

surgical patients, variable indications for surgery and

surgical techniques, and inconsistent approaches to

postoperative analgesia (e.g., limited use of multimodal

regimens).12 The objective of this trial was to evaluate the

analgesic effects of adding a continuous local anesthetic-

based epidural infusion to standard systemic multimodal

analgesia and to compare the results with use of systemic

multimodal analgesia alone in a patient population

undergoing lumbar decompression and fusion. Specifically,

our primary objective was to determine if the addition of

epidural analgesia to systemic multimodal analgesia would

reduce opioid consumption over the first 48 hr

postoperatively when compared with systemic multimodal

analgesia alone. Our secondary objective was to assess and

compare the effects of each regimen on pain scores,

opioid-related side effects, and discharge time from hospital.

Methods

The study was conducted at Toronto Western Hospital, part

of University Health Network, a tertiary care academic

health sciences centre. The University Health Network

Research Ethics Board approved the study (January 2008),

and all patients provided written and informed consent.

Adults (18-80 years of age and American Society of

Anesthesiologists [ASA] status I-III) who were scheduled

to undergo primary one- or two-level lumbar decompression

and fusion for pain due to spondylolisthesis were eligible for

the study. Exclusion criteria included the inability to provide

informed consent, revision fusion, body mass index [ 40,

language barrier, allergy to local anesthetics, bleeding

diathesis, pregnancy, high-dose opioid use (defined as

preoperative opioid consumption [ 250 mg oral morphine

equivalent per day), preexisting neurologic deficits (defined

as sensory or motor deficit corresponding to the spinal level

of surgery), and history of drug addiction. All patients were

recruited from the practice of a single spine surgeon

(Y.R.R.). Patients were recruited in the surgeon’s

preoperative clinic by a research coordinator.

A randomization sequence was created by an independent

statistician using www.randomization.org. The randomiza-

tion sequence was stratified by number of surgical levels (one

or two) and sex. Permuted blocks of four were used within

each stratum. The randomization list was kept in the

possession of the independent research pharmacy at Toronto

Western Hospital. The pharmacy created sequentially

numbered identical kits containing all study materials. When

the postoperative analgesic regimen was initiated, the next

kit in the sequence was used. The research coordinator and

all investigators, participants, care providers, outcome

assessors, and data analysts were blinded to treatment group.

All patients were pre-medicated with oral acetaminophen

(1,000 mg age \ 70 yr, 650 mg age [ 70 yr) and oral

gabapentin (600 mg age \ 70 yr, 300 mg age [ 70 yr) as

per our institutional preventive analgesic strategy.

Subsequently, all patients underwent a standardized

induction technique using midazolam 0.03 mg�kg-1

fentanyl 2 lg�kg-1, and propofol 2-3 mg�kg-1 iv.

Endotracheal intubation was facilitated with rocuronium

0.6 mg�kg-1 iv; ventilation was maintained with an inspired

oxygen concentration of 0.5, and general anesthesia was

maintained with desflurane at 1.0 minimum alveolar

concentration. Patients were treated with forced-air

S. Choi et al.

123

warming, and intraoperative analgesia was provided with

titrated intravenous hydromorphone boluses. Muscle

relaxation was reversed using neostigmine 50 lg�kg-1 iv

and glycopyrrolate 10 lg�kg-1 iv, while granisetron 1 mg iv

was used for antiemetic prophylaxis.

With the exception of the number of levels (stratified to

one- or two-level fusion), the surgical procedure was

identical for all patients in order to reduce the potential

confounding effect of surgical morbidity on acute

postoperative pain and narcotic requirements. All patients

underwent decompression and fusion with port access and

instrumentation (METRxTM fixed 22-mm tubular retractor

and the SEXTANTTM percutaneous pedicle screw-rod

system, Medtronic, Memphis, TN, USA). Surgery involved

a paramedian muscle-splitting approach with

decompression, transforaminal lumbar interbody fusion,

placement of a single interbody device (CAPSTONETM,

Medtronic, Memphis, TN, USA), and stabilization using

bilateral percutaneous segmental pedicle screw and rod

fixation. The single surgeon (Y.R.R.) had extensive

experience with this technique, which provides consistent

exposure to morbidity, surgical time, and blood loss.

After closure of the surgical wound, the surgeon (Y.R.R.)

introduced a single-orifice 19G epidural catheter (Arrow,

Teleflex Medical, Markham, ON, Canada) in a sterile fashion

using a loss of resistance to air technique at one vertebral

level above the operative site. The surgeon then threaded the

catheter three centimeters into the epidural space with

fluoroscopic guidance. Proper placement and catheter tip

position inside the epidural space was confirmed using 3 mL

of Omnipaque� (GE Healthcare, Mississauga, ON, Canada)

dye visualized by real-time fluoroscopy.

The postoperative analgesic regimen was initiated shortly

after patient arrival in the postanesthesia care unit (PACU)

following motor function assessment by the surgeon.

Patients randomized to the LA group received an initial

epidural bolus of hydromorphone 0.6 mg diluted in 0.9%

saline 3 mL followed by an infusion of 0.1% bupivacaine

with hydromorphone 15 lg�mL-1 at 6 mL�hr-1 for 48 hr.

Patients in the NS group received an initial bolus of 0.9%

saline 3 mL followed by an infusion of 0.9% saline at

6 mL�hr-1. All epidural solutions were prepared in a sterile

fashion by our independent research pharmacy according to

patient group allocation. The solutions were delivered to the

PACU in 5 mL syringes containing the initial study bolus

solution and 250 mL container bags filled with the study

infusion solution. To maintain blinding and allocation

concealment, the epidural solutions were labelled with the

patients’ initials, study number (1-39), and a line printed with

‘‘0.6 mg hydromorphone in 3 mL of saline or 3 mL saline

placebo’’ on the syringes and ‘‘0.1% bupivacaine with 15 lg

of hydromorphone per mL or saline placebo’’ on the

container bags.

All patients received an intravenous patient-controlled

analgesia (PCA) device programmed to deliver a bolus

dose of 0.2-0.4 mg iv hydromorphone, lockout of five

minutes, and a maximum dose of 10 mg over four hours.

Additionally, all patients received oral acetaminophen

1,000 mg every six hours (650 mg for age [ 70 yr) and

oral gabapentin 200 mg every eight hours (100 mg for

age [ 70 yr) as part of a multimodal analgesic regimen.12

Nonsteroidal anti-inflammatory medications, however,

were not used due to concerns of non-union and bleeding

in the setting of spinal fusion.13 After initiation of the

epidural infusion, inadequate pain control (verbal numeric

rating scale [VNRS] C 5) was addressed in a standardized

fashion regardless of group allocation, i.e., the epidural

infusion rate was increased by 2 mL�hr-1 and the

intravenous PCA bolus dose was increased by 0.2 mg.

This intervention was repeated again if deemed necessary

by the attending anesthesiologist on the Acute Pain Service

(APS) who was blinded to patient group allocation. Spinal

sensory block levels were not routinely assessed in an

effort to preserve patient and assessor blinding. The

epidural catheter was removed 48 hr after initiation of

the infusion.

All patients were treated on the same postoperative ward

and received corresponding nursing care, mobilization

protocol (starting postoperative day 1), and physiotherapy

services.

The APS staff continued to visit all patients twice daily.

As per our institutional practice, patients no longer requiring

intravenous PCA were offered controlled-release and/or

immediate-release oxycodone or hydromorphone at the

discretion of the attending anesthesiologist on the APS in

order to achieve a VNRS pain score of B 4. In the event of

inadequate pain control (VNRS pain score[ 7), intravenous

PCA was maintained. Upon discharge from hospital, patients

received one of three oral analgesic preparations to be taken up

to every four hours as needed: Tylenol #3� (acetaminophen

300 mg/codeine, 30 mg/caffeine, 15 mg per tablet), Percocet�

(acetaminophen 325 mg, oxycodone HCl, 5 mg per tablet), or

acetaminophen with immediate-release hydromorphone if

intolerant to codeine. To facilitate data analysis, equian-

algesic conversion ratios were employed according to the

general monograph for opioids in the Canadian Pharmacists’

Association Compendium of Pharmaceuticals and Specialties

(hydromorphone:morphine = 1:5, oxycodone:morphine =

2:3, intravenous:oral = 1:3).A As described previously, oral

acetaminophen and gabapentin were continued until discharge

from hospital.

A Compendium of Pharmaceuticals and Specialties; 2011.

Epidural analgesia after lumbar fusion

123

Outcome measures and assessment

Patients were assessed at the following time points: (i)

15 min after arrival in the PACU (immediately prior to the

epidural bolus); (ii) twice daily on postoperative days 1 and 2

(0800 hours and 1600 hours); and (iii) once daily

(0800 hours) until discharge. The primary outcome

measure was defined as cumulative opioid consumption at

48 hr. Secondary outcomes collected at each assessment

included: pain at rest and with mobilization (VNRS from

0 = no pain to 10 = worst pain imaginable); heart rate

(bradycardia defined as heart rate \ 55 beats�min-1) at any

time since the last assessment; blood pressure (hypotension

defined as systolic blood pressure\ 100 mmHg) at any time

since the last assessment; presence of nausea and vomiting at

any time since the last assessment; sedation (four-point

scale: 0 = awake and alert; 1 = mild - easy to arouse;

2 = moderate - frequently drowsy and easy to arouse,

3 = severe - somnolence and difficult to arouse) at any time

since the last assessment; presence of pruritus at any time

since the last assessment; urinary retention (inability to void

[ 24 hr after epidural removal); time to assisted and

unassisted ambulation; patient satisfaction with analgesic

modality (Quality of Recovery Score administered on

postoperative day 2 after removal of the epidural

catheter);14 and time to discharge readiness (date of

discharge order from patient’s chart).

All study patients completed baseline questionnaires with

respect to medical history, pain, and functional disability

(Oswestry Disability Index [ODI]), as well as surgical

expectation as per the surgeon’s (Y.R.R) standard clinical

practice.15 The surgical expectation score is not a validated

measure but standard information that is routinely collected

by our surgical department (Appendix). There were no

changes to the study protocol or outcome assessments during

the trial period.

Statistical analysis

In a retrospective review of 20 consecutive patients

undergoing port access lumbar decompression and fusion

with intravenous PCA at Toronto Western Hospital prior to

the current study, results revealed a mean cumulative

opioid consumption of 562.8 mg oral morphine equivalent

up to and including postoperative day 2. Based on a priori

discussions between the investigators and past experience

with epidural analgesia, we aimed to detect a 50%

reduction in cumulative opioid consumption at 48 hr.

Assessed for eligibility(n=79)

Excluded (n=40)• Did not meet inclusion criteria (n=3)• Declined participation (n=37)

Randomized (n=39)

Allocated to CEA (n=20)• Received allocated intervention (n=18)• Did not receive allocated intervention (n=2):

Intractable nausea, epidural infusion without opioids used (see text)Epidural discontinued at patient’s request (see text)

Allocated to NS (n=19)• Received allocated intervention (n=17)• Did not receive allocated intervention (n=2):

Epidural catheter dislodged prior to initiation of infusion (see text)Undisclosed illicit drug use, patient removed from study (see text)

Lost to follow up (n=0)

Analyzed (n=20) Analyzed (n=18)

Lost to follow up (n=0)

Fig. 1 CONSORT diagram

detailing screened, randomized,

and analyzed patients,

n = number of patients

S. Choi et al.

123

Therefore, assuming a standard deviation of 200.72 mg

(based on our retrospective data), we estimated that a

minimum of 16 patients would be required for

randomization. We set type I error a = 0.05 (two-sided)

and type II error b = 0.2. Due to the small sample size,

there was no planned interim analysis or early stopping rule.

Computerized statistical analysis was performed using

SPSS� 18 (IBM, Armonk, NY, USA). Differences between

groups for continuous variables were analyzed using the

Student’s two-sample t test, while categorical variables

were analyzed using the Chi square or Fisher’s exact test if

any expected cell size was less than five. Statistical tests

were two-sided.

Results

Thirty-nine of the 79 eligible patients approached consented to

participate in the study during January 2008 to April 2011

(Fig. 1). Each patient was followed in hospital until they were

discharged home. The trial was stopped once the planned

number of patients were recruited. Twenty participants were

randomized to the LA group and 19 were randomized to the

NS group. One patient randomized to the NS group was

withdrawn from the study due to illicit drug use that was not

disclosed by the patient preoperatively. One patient

randomized to the LA group requested discontinuation of

the intervention and removal of the epidural catheter because

of anxiety related to the sensation of sensory/motor blockade.

One patient randomized to the LA group suffered intractable

nausea; this patient was unblinded and the epidural study

solution was changed to 0.2% ropivacaine without

hydromorphone. One patient randomized to the NS group

experienced an accidental dislodgement of the epidural

catheter during transfer from the operating room table to the

bed; epidural solution was not administered to this patient.

These latter three patients consented to continued data

collection and analysis. In total, 20 patients were analyzed in

the LA group and 18 in the NS group.

Patient characteristics were similar between groups with

respect to age, sex, body mass index, ASA physical status,

number of levels decompressed, preoperative baseline pain

and opioid use, expectations from surgery, ODI, and

duration of surgery (Table 1).

At 48 hr, the mean (SD) cumulative opioid consumption

was 249.3 (143.3) mg in the NS group and 184.7 (208.1)

mg in the LA group (mean difference 64.6 mg; 95%

confidence interval (CI) -54.3 to 183.5; P = 0.27)

(Fig. 2). There were no differences in intravenous PCA

hydromorphone consumption in isolation (Table 2). There

were no differences in the self-reported Quality of

Recovery Score or the number of days to assisted

ambulation, unassisted ambulation, and time to discharge

from hospital (Table 2). Postoperative pain scores from the

PACU onwards (VNRS at rest) and postoperative day 1

onwards (VNRS at movement) are presented in Fig. 3.

Epidural and opioid-related side effects were similar

between groups (Table 3).

Discussion

This study was designed to evaluate the effects of

continuous epidural analgesia with a local anesthetic and

opioid solution in a homogeneous surgical population with

concomitant systemic multimodal analgesia following

Table 1 Patient characteristics

LA Group

(n = 20)

NS Group

(n = 18)

Age, years 57 (13) 59 (13)

Sex (M/F), n 7/13 6/12

BMI, kg�m-2 28 (5) 29 (6)

ASA I/II/III, n 1/11/8 0/11/7

Levels Decompressed (1/2), n 14/6 13/5

Preoperative baseline pain, VNRS 5 (3) 5 (3)

Preoperative mean daily morphine, mg 18 (4) 8 (16)

Preoperative ODI 43 (15) 41 (13)

Preoperative symptom relief expectation 6 (1) 4 (1)

Surgical duration, min 202 (13) 199 (21)

Data presented as number of patients or mean (SD), ASA =

American Society of Anesthesiologists (physical status); BMI =

body mass index, ODI = Oswestry Disability Index; VNRS = verbal

numeric rating scale

Preoperative baseline pain and average daily oral morphine equivalent

consumption assessed at time of preoperative anesthesia clinic assessment

249.3 184.7

-50

0

50

100

150

200

250

300

350

400

450

mg

NS group LA group

Difference 64.6 mg, 95%CI: -54.3 to 183.5 mg, P= 0.27

Fig. 2 Cumulative 48 hr oral morphine consumption. Data presented

as mean with bars denoting standard deviation

Epidural analgesia after lumbar fusion

123

lumbar decompression and fusion. We observed a mean

reduction in average cumulative opioid consumption of

approximately 64.6 mg at 48 hr; however, this estimate

was imprecise (95% CI: -54.3 to 183.5), thus no definitive

conclusion could be made about the efficacy of adjuvant

epidural anesthesia. Most similar studies published

previously did not employ opioid-sparing adjuncts.2-5,8

One study included standing order acetaminophen;9 one

study included a nonsteroidal anti-inflammatory drug

(NSAID) on an as needed basis,7 and one study included

Table 2 Secondary outcomes

NS Group mean

(SD) (n = 18)

LA Group mean

(SD) (n = 20)

Mean Difference (95% confidence

interval) P value

Intravenous-PCA hydromorphone (mg)

24 hr 8.6 (6.8) 5.8 (7.6) 2.8 (-1.9 to 7.5) P = 0.24)

48 hr 15.6 (11.9) 12.3 (12.1) 3.3 (-5.4 to 12.0) P = 0.44)

Quality of Recovery 13.7 (2.7) 14 (3.3) -0.3 (-2.3 to 1.7) P = 0.74)

Days to assisted ambulation 1.7 (1.2) 1.9 (1.1) -0.2 (-1.0 to 0.6) P = 0.64)

Days to unassisted ambulation 4.0 (1.8) 3.9 (2.) 0.1 (-1.2 to 1.4) P = 0.88)

Days to discharge readiness 4.8 (1.6) 5.2 (2.6) 0.4 (-1 to 1.8) P = 0.6)

PCA = patient-controlled analgesia

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

PACU POD1 08h00 POD1 16h00 POD2 08h00 POD 2 16h00 POD3 08h00

VN

RS

NS group LA group

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

PACU POD1 08h00 POD1 16h00 POD2 08h00 POD 2 16h00 POD3 08h00

VN

RS

NS group LA group

A

B

Fig. 3 Line graph of verbal

numeric rating scale (VNRS)

pain scores. Panel A) VNRS at

rest, Panel B) VNRS with

movement. Data presented as

median [interquartile range]

S. Choi et al.

123

acetaminophen plus a NSAID on an as needed basis10

(Table 4). Inconsistent systemic analgesic protocols may

partially explain why the optimal postoperative regimen

following lumbar fusion and decompression has not yet

been determined.

The strength of the present trial stems from the homogeneity

of both diagnosis and procedure with the presence of a

standardized multimodal analgesic protocol. Previous studies

investigating the role of epidural analgesia after spine surgery

have been limited by methodological shortcomings, including

heterogeneity in diagnosis and procedure,5,8,9 non-standardized

analgesic co-intervention,9,10 either extremely high4 or

extremely low5,8 doses of epidural local anesthetic, and

significant loss to follow-up (patients removed from study

due to protocol violations)4,8,9 (Table 4). Predictably, studies

reporting issues with transient sensorimotor deficits were those

utilizing high infusion rates.2-4 None of the previous studies

reported issues with hemodynamic instability.

Several procedural factors related to the epidural may

have affected our results. First, while our epidural infusion

rate was thoughtfully selected in order to strike a balance

between analgesia and undesired motor blockade, it is

possible that this rate was too low. Indeed, previous studies

determining the efficacy of epidural analgesia for open spine

surgery used continuous infusion rates up to 14 mL�hr-1

along with a patient-controlled epidural bolus feature.3,4 We

have had a similar experience using a catheter placed directly

through the decompression space; however, in our view,

such high rates may have been required to compensate for the

loss of local anesthetic solution through the traditional

surgical wound. Moreover, while infusion rates higher than

6 mL�hr-1 provide effective analgesia, our institutional

experience is that these rates produce undesirable side effects

and motor block in the setting of lumbar fusion.

Consequently, we switched to a loss of resistance

technique at a cephalad non-decompressed level. The use

of a continuous infusion technique may not have provided as

effective analgesia as a continuous infusion combined with a

patient-controlled epidural analgesia (PCEA) bolus feature;

however, our institutional experience with PCEA (infusion

of 8 mL�hr-1 with a bolus of 2-4 mL every 30 min as

required) culminated in a disproportionate number of

patients with clinically significant hypotension. Finally,

under the present study conditions, the use of PCEA may

have led to patient confusion with two separate patient-

controlled devices.

We recognize that our study design was based on

assumptions that ultimately did not reflect the conditions of

the trial. The retrospective data used to calculate our

sample size were collected in the absence of a standard

multimodal analgesia regimen. The trial was designed to

detect a 50% reduction in oral morphine consumption from

a historical level of approximately 560 mg; the morphine

consumption in the control group in this trial was

approximately 250 mg. The confidence interval for the

opioid sparing effects of epidural analgesia added to

multimodal analgesia was very wide, from 54.3 mg in

favour of the control group to 183.5 mg in favour of

epidural analgesia. Thus, we cannot rule out the possibility

of a 50% reduction (*125 mg) in morphine consumption

with the addition of an epidural anesthetic. Furthermore,

we recognize that the decision to use the estimated opioid

use and variance from our retrospective data in our sample

size calculation may have contributed to inflating the

imprecision in our estimate of effect.16

In summary, we observed that continuous epidural

analgesia combined with systemic multimodal analgesia

following one- or two-level lumbar decompression and

fusion resulted in a reduction in opioid consumption of

64.8 mg oral morphine equivalent, but this was an

imprecise estimate (95% CI: -54.3 to 183.5). Based on

this study, the routine use of continuous epidural analgesia

to reduce postoperative opioid consumption is not yet

warranted. Our findings suggest that the optimal regimen

for postoperative pain following one- or two-level lumbar

decompression and fusion has yet to be determined.

Table 3 Epidural/opioid side effects

NS Group

(n = 18)

LA Group

(n = 20)

Nausea/Emesis

Day 1 5/18 10/20

Day 2 4/18 6/20

Day 3 4/18 3/20

Hypotension

Day 1 0/18 0/20

Day 2 0/18 0/20

Day 3 0/18 0/20

Bradycardia

Day 1 0/18 0/20

Day 2 0/18 0/20

Day 3 0/18 0/20

Urinary retention 11/18 16/20

Pruritus 12/18 13/20

Confusion

Day 1 0/18 1/20

Day 2 3/18 1/20

Day 3 0/18 1/20

Sedation score, mean (SD)

Day 1 0.7 (0.8) 0.2 (0.6)

Day 2 0.4 (0.9) 0.2 (0.5)

Day 3 0.3 (0.8) 0.1 (0.3)

Data presented as number of patients or mean (SD)

Epidural analgesia after lumbar fusion

123

Tab

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Com

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est

udie

sas

sess

ing

epid

ura

lan

alges

iaw

ith

loca

lan

esth

etic

vs

syst

emic

opio

ids

afte

rsp

ine

surg

ery

Auth

or/

Yea

rS

tudy

Des

ign

Jadad

Sco

ren

Gro

ups

(n)

Dia

gnose

sS

urg

ical

Pro

cedure

sS

pxin

alL

evel

s(n

)

Choi

2013

RC

T5

38

CE

I?

IV-P

CA

(20)

IV-P

CA

(18)

Spondyl

Min

imal

lyIn

vas

ive

Post

erio

r

inst

rum

ente

dfu

sion

Lum

bar

(1-2

)

Klu

ba

2010

10

352

CE

I(2

9)

IV-P

CA

(23)

Deg

ener

ativ

edis

cdis

ease

Post

erio

rin

stru

men

ted

fusi

on

Lum

bar

(1-2

)

Cat

a2008

5R

ET

N/A

245

PC

EA

(134)

IV-P

CA

(111)

Spin

alst

enosi

s,S

pondyl

•L

amin

ecto

my

±post

erio

r

inst

rum

ente

dfu

sion

•V

erte

bra

lost

eoto

my

Thora

cic,

Lum

bar

(N/A

)

Sch

enk

2006

4R

CT

472

PC

EA

(28)

IV-P

CA

(30)

Spondyl

Com

bin

edan

teri

or/

post

erio

rfu

sion

Lum

bar

(1-2

)

Blu

men

thal

2005

2R

CT

330

CE

I(1

5)

IV-P

CA

(15)

Thora

cic

idio

pat

hic

scoli

osi

sP

ost

erio

rsc

oli

osi

sco

rrec

tion

and

fusi

on

Thora

cic

(7-1

1)

Gott

schal

k2004

3R

CT

530

CE

I(1

3)I

V-P

CA

(13)

N/A

Post

erio

rin

stru

men

ted

fusi

on

Lum

bar

(N/A

)

Fis

her

2003

9R

CT

586

PC

EA

(36)I

V-P

CA

(38)

Deg

ener

ativ

edis

cdis

ease

,S

pondyl,

Spin

alin

stab

ilit

y

Post

erio

rin

stru

men

ted

fusi

on

±

lam

inec

tom

y

Lum

bar

(1-2

)

Cas

sady

2000

7R

CT

233

CE

I(1

4)I

V-P

CA

(15)

Idio

pat

hic

scoli

osi

sP

ost

erio

rin

stru

men

ted

fusi

on

Thora

cic/

Lum

bar

(10-1

5)

Cohen

1997

8R

CT

354

CE

I?IV

-PC

A(2

1)I

V-P

CA

(21)

Deg

ener

ativ

edis

cdis

ease

,S

pondyl.

,

Spin

alin

stab

ilit

y,

Spin

alst

enosi

s

Post

erio

rin

stru

men

ted

fusi

on

Thora

cic/

Lum

bar

(1-6

)

Auth

or/

Yea

rE

pid

ura

lC

athet

erT

echniq

ues

Anal

ges

icC

o-i

nte

rven

tions

Res

ult

sR

emar

ks

Inse

rtio

nL

oca

tion

Confi

rmP

CE

AB

olu

sIn

fusi

on,

rate

,dura

tion

Choi

2013

Per

cuta

neo

us,

1le

vel

above

fusi

on,

3cm

into

epid

ura

l

spac

e

LO

R,

Dye

None

Bupi

0.1

%?

Hydro

morp

h

15

lg�m

L-

1A

ceta

min

ophen

,

Gab

apen

tin

No

dif

fere

nce

show

nbet

wee

ngro

ups

Klu

ba

2010

10

Thro

ugh

surg

ical

sight,

fusi

on

level

,tu

nnel

led

late

ral,

tip

3

cmin

toep

idura

lsp

ace

Dir

ect

vis

ion

None

Ropi

0.2

%?

Suf

0.4

lg�m

L-

1

8m

L�h

r-1,

28.3

-61.7

hr

Par

acet

amol

and

Dic

lofe

nac

prn

CE

I,re

duce

dtr

ansd

erm

alfe

nt

(P=

0.0

45)

•N

on-b

linded

Cat

a2008

5T

hro

ugh

surg

ical

site

,fu

sion

level

,ti

p4-6

cmin

toep

idura

l

spac

e

Dir

ect

vis

ion

None

Bupi

0.0

625-0

.1%

?F

ent

2-5

lg�m

L-

1R

ate

N/A

Dura

tion

N/A

Fen

tor

morp

hin

eor

hydro

morp

hone

prn

•P

CE

A,

reduce

dpai

n(P

=0.0

01)

•P

CE

A,

reduce

dopio

id(P

\0.0

01)

•R

etro

spec

tive

revie

w

Sch

enk

2006

4T

hro

ugh

surg

ical

site

,1

level

above

fusi

on,

tip

3-6

cmin

to

epid

ura

lsp

ace

Dir

ect

vis

ion

5m

LR

opi

0.1

25%

?S

uf

1l

g�m

L-

1

14

mL�h

r-1,

72

hr

Met

amiz

ole

prn

•P

CE

A,

reduce

dpai

n(P

\0.0

001)

•P

CE

A,

reduce

dopio

id(P

\0.0

001)

•14

pat

ients

rem

oved

from

study

Blu

men

thal

2005

2T

wo

cath

eter

s,th

rough

surg

ical

site

,ti

ps

1le

vel

cephal

adan

d

caudad

tofu

sion

level

s

LO

R,

Dye

None

Ropi

0.3

%4-1

0m

L�h

r-1,

each

cath

eter

init

iate

d,

PO

D1

72

hr

None

•C

EI,

reduce

dpai

n(P

\0.0

5)

•C

EI,

reduce

dopio

id(P

\0.0

5)

•C

EI,

reduce

dN

V(P

\0.0

5)

•N

on-b

linded

Gott

schal

k2004

3T

hro

ugh

surg

ical

site

,m

iddle

of

fusi

on

level

s,tu

nnel

led

late

ral,

3cm

into

epid

ura

lsp

ace

LO

R,

Dir

ect

vis

ion

None

Ropi

0.1

%14

mL�h

r-1,

72

hr

None

•C

EI,

reduce

dpai

n(P

\0.0

5)

•C

EI,

reduce

dopio

id(P

\0.0

5)

•4

pat

ients

rem

oved

from

study

Fis

her

2003

9T

hro

ugh

surg

ical

site

,fu

sion

level

,ti

p10

cmin

toep

idura

l

spac

e

Dye

2-4

mL

q10

min

Bupi

0.1

%?

Fen

t5

lg�m

L-

1?

Epi

1l

g�m

L-

1,2

-8m

L�h

r-1

Dura

tion

N/A

Ace

tam

inophen

,

Ket

amin

e(i

f

pre

-op

morp

hin

e

[60

mg)

No

dif

fere

nce

bet

wee

ngro

ups

•12

pat

ients

rem

oved

from

study

•11

pat

ient

cross

over

s

•8

pat

ients

wit

h

conta

min

ated

dat

a

S. Choi et al.

123

Acknowledgement The authors sincerely thank Mr. Michael Yang

(BSc) for his help with data collection.

Funding PSI Foundation resident research grant (S.C. and R.B.);

Toronto General and Western Hospital Foundation Educational Grant

(Y.R.R. and O.P.); R.B. is supported by the Merit Award Program,

Department of Anesthesia, University of Toronto.

Financial support This project was supported by a Physicians’

Services Incorporated Resident Research Grant awarded to the first

author (S.C., supervisor R.B. $19,500). Funding was also received

from the Minimal Access Ambulatory Spine Surgery (MAASS)

Research and Education Project, Toronto General and Western

Hospital Foundation (Y.R.R., $6,000). The funding agencies had no

role in protocol development, data collection/analysis, or preparation

of the manuscript.

Conflicts of interest None declared.

Appendix- Standard preoperative questionnaire

completed by patients in surgeon’s (Y.R.R.) clinic

1. What results do you expect from your treatment

(Circle one response on each line)

2. If you had to spend the rest of your life with the

symptoms you have right now, how would you feel

about it?

Tab

le4

conti

nued

Auth

or/

Yea

rE

pid

ura

lC

athet

erT

echniq

ues

Anal

ges

icC

o-i

nte

rven

tions

Res

ult

sR

emar

ks

Inse

rtio

nL

oca

tion

Confi

rmP

CE

AB

olu

sIn

fusi

on,

rate

,dura

tion

Cas

sady

2000

7T

hro

ugh

surg

ical

site

,T

6/7

,

tunnel

led

late

ral,

tip

2.5

cm

into

epid

ura

lsp

ace

Dir

ect

vis

ion

None

Bupi

0.2

5%

?F

ent

2.5

lg�m

L-

10.2

8m

L�k

g-

1�h

r-1

Ket

oro

lac

prn

for

VR

SC

5N

odif

fere

nce

bet

wee

ngro

ups

•3

pat

ients

rem

oved

from

study

Cohen

1997

8T

hro

ugh

surg

ical

site

,2-3

level

s

cephal

adto

fusi

on

Dir

ect

vis

ion

None

Bupi

0.0

625%

?M

orp

hin

e

40

lg�m

L-

10.2

8m

L�k

g-

1�h

r-1

None

CE

I,re

duce

dopio

id(P

=0.0

022)

•14

pat

ients

rem

oved

from

study

Bupi

=bupiv

acai

ne;

CE

I=

conti

nuous

epid

ura

lin

fusi

on;

Epi

=ep

inep

hri

ne;

Fen

t=

fenta

nyl;

IV-P

CA

=in

trav

enous

pat

ient

contr

oll

edan

alges

ia;

LO

R=

loss

of

resi

stan

ce;

n=

num

ber

of

random

ized

pat

ients

inst

udy;

n=

num

ber

of

pat

ients

anal

yze

din

each

gro

up

or

surg

ical

level

s;N

/A=

not

appli

cable

or

not

indic

ated

inst

udy;

PC

EA

=pat

ient

contr

oll

edep

idura

lan

alges

ia;

Per

cut

=per

cuta

neo

us;

PO

D=

post

oper

ativ

eday

;

PO

NV

=post

oper

ativ

enau

sea

and

vom

itin

g;

RC

T=

random

ized

contr

oll

edtr

ial;

RE

T=

retr

osp

ecti

ve

revie

w;

Ropi

=ro

piv

icai

ne;

Spondyl

=sp

ondylo

list

hes

is;

Suf

=su

fenta

nil

;V

RS

=ver

bal

rati

ng

scal

e

Not

at all

likely

Slightly

likely

Somewhat

likely

Very

likely

Extremely

likely

Not

applicable

Relief from

symptoms

(pain,

stiffness,

swelling,

numbness,

weakness,

instability)

1 2 3 4 5 6

To do more

everyday

household

activities or

yard activities

1 2 3 4 5 6

To sleep more

comfortably

1 2 3 4 5 6

To go back to

my usual job

1 2 3 4 5 6

To exercise and

do

recreational

activities

1 2 3 4 5 6

To prevent

future

disability

1 2 3 4 5 6

Very

Dissatisfied

Somewhat

dissatisfied

Neutral Somewhat

satisfied

Very

satisfied

Epidural analgesia after lumbar fusion

123

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S. Choi et al.

123