HW

ORIGINAL ARTICLE � HIP – ANESTHESIA

A randomized controlled trial of postoperative analgesia following total knee replacement: transdermal Fentanyl patches versus patient controlled analgesia (PCA)

M. J. Hall1 • S. M. Dixon2 • M. Bracey3 • P. MacIntyre4 • R. J. Powell3 •

A. D. Toms3

Received: 13 November 2014 / Accepted: 12 February 2015 / Published online: 11 March 2015

� Springer-Verlag France 2015

Abstract

Background This randomized controlled trial compared a

standard patient controlled analgesic (PCA) regime with a

transdermal and oral Fentanyl regime for post-operative

pain management in patients undergoing total knee

replacement.

Methods One hundred and ninety-six patients undergoing

total knee replacement were recruited. Pre- and post-op-

eratively Visual Analogue Score (VAS), Oxford Knee

Score, Health Anxiety and Depression Score and Brief Pain

Inventory Score were completed. According to the day 1,

VAS score patients were randomly allocated to either a

PCA regime or a Fentanyl transdermal/oral regime. Patient

reported outcomes were measured until the patients were

discharged.

Results The results demonstrate that in terms of analgesic

effect, day of discharge and side effect profile the two

regimes are comparable.

Conclusions We conclude that a Fentanyl transdermal

regime provides adequate analgesic effect comparable to a

standard PCA regime in conjunction with a low side effect

profile. Using a transdermal analgesic system provides ef-

ficient continuous delivery enabling a smooth transition

from hospital to home within the first week. Transdermal

Fentanyl provides an alternative analgesic regime that can

provide an equivalent analgesic effect so as to enable a

satisfactory outcome for the patient in terms of function

and pain.

Level of evidence II.

Keywords Total knee replacement � Post-operative analgesia � Patient controlled analgesia � Fentanyl patches

Introduction

Knee replacement surgery has proved a successful and

cost-effective method for relieving pain and restoring

function in patients with osteoarthritis [1]. However, pain

management after knee replacement surgery remains a

significant problem, with patients reporting this as a major

concern prior to surgery [2]. Implementing relevant pre-

operative screening methods may facilitate the identifica-

tion of individuals at high risk of experiencing high post-

operative pain [3]. Despite recent advances in the aetiology

of pain, improved pain treatments and the development of

clinical guidelines for pain assessment, the under-treatment

of post-operative pain remains a challenge to both surgeon

and anaesthetist. Recent studies have clearly demonstrated

that patient satisfaction following total knee replacement is

multifactorial with the most significant predictor of dis-

satisfaction being a painful total knee replacement [1].

Providing effective pain relief in the post-operative pe-

riod is essential to enable early mobilisation and reha-

bilitation, minimise immobility-related complications,

maximise functional outcome and reduce hospital stay.

Many different methods of delivering adequate analgesia

are currently employed but one of the most established is

intravenous (IV) patient controlled analgesia (PCA). This

provides the benefit of self-titrated IV opioid medication

& M. J. Hall matthewhall74@me.com

1 Yeovil District Hospital, Higher Kingston,

Yeovil BA21 4AT, UK

2 Royal Cornwall Hospital, Truro, UK

3 Royal Devon & Exeter Hospital, Exeter, UK

4 Nelson Bay District Hospital, Nelson, New Zealand

123

Eur J Orthop Surg Traumatol (2015) 25:1073–1079

DOI 10.1007/s00590-015-1621-6

enabling active participation in the patient’s own post-op-

erative management compared to a more generic, orally

delivered analgesia. The disadvantages are the cost of PCA

pumps along with the monitoring required and nursing time

to manage the systems appropriately.

The literature provides no clear answers as to the best

method of post-operative pain relief, with studies showing

PCA [4] and regional techniques [5, 6] both providing good

analgesia to enable rehabilitation. The major drawback of

morphine can be the side effect profile, including nausea,

constipation and itching, whereas with regional analgesia

the reliability and duration of action can be problematic.

Fentanyl has formed the mainstay of intra-operative

analgesia and has many beneficial features. In the lozenge

form, it has a very rapid onset and can reach peak activity

within 20 min compared to 40–60 min for oral morphine

[7]. For this reason, the main clinical application of oral

fentanyl lozenges is in the field of oncology for manage-

ment of breakthrough pain.

The aim of this randomized controlled study was to

compare two analgesic regimes, PCA and Fentanyl (in a

transdermal and oral form) and demonstrate that a trans-

dermal Fentanyl patch can provide comparable post-op-

erative analgesia to a standard PCA regime in terms of pain

and side effect profile without compromising rehabilitation

and discharge times. Post-operatively on day 1, we divided

patients into a low and high pain group based on a pain

score to see if this enabled an accurate prediction of pain

requirements during the subsequent post-operative period.

Patients and methods

All patients undergoing a unilateral total knee replacement

at the Royal Devon and Exeter Hospital were invited to

take part in the trial, which included all surgeons per-

forming knee replacement surgery within the trust. Patients

were excluded from the study if they were unable to walk

twenty metres or climb three stairs for any reason other

than pain in the affected joint, trauma and refusal or in-

ability to give valid consent. Pre-operatively the study

group completed the Oxford Knee Score (OKS) [17],

Health Anxiety Depression Score (HADS) and Brief Pain

Inventory Score (BPI). Participants in the trial were pre-

scribed paracetamol (1 g QDS), an anti-inflammatory

(Diclofenac 50 mg BD) and oral morphine (10–20 mg two

hourly) as required.

Patients were given a pain diary on day 1 and asked to

score the pain on movement of the limb using a ten-point

Visual Analogue Score (VAS). If this score was 6/10 or

more they were entered into the high pain group (HPG),

and less than six entered the low pain group (LPG). An

independent statistician using a sealed envelope technique

carried out randomization of the HPG into the two treat-

ment arms. The LPG remained on the routine analgesic

regime. In the HPG, patients were randomized to either

intravenous morphine administered through a PCA pump,

or a Fentanyl patch with oral Fentanyl in the form of a

lozenge that can be taken two hourly prior to exercise or

for breakthrough pain. The doses of morphine in the PCA

were 1 mg bolus with a 5 min lockout and no 4-h limit or

background infusion. The doses of Fentanyl patch were

12.5 mcg for patients over 65 years and 25 mcg for pa-

tients under 65 years with lozenges up to 400 mcg for

breakthrough pain and up to five 200 mcg lozenges,

whilst waiting for the patch to reach therapeutic plasma

levels. The lozenges were titrated against signs of

lightheadedness.

Each day until discharge, patients attempted standard

physiotherapy tasks as part of their physiotherapy regime

and then scored their pain using the VAS which is scored

zero to ten (where the lower the score the less the patient’s

pain). Patients were also asked to complete the BPI score

with 1–4 being mild, 4–6 moderate and 7–10 severe pain.

These scores were completed for worst pain, least pain,

average pain, pain currently, pain on activity, pain effect on

mood, pain on walking, pain whilst at work, pain affect on

relations, pain whilst sleeping and pain effect on enjoy-

ment. Pain assessment was carried out on a daily basis until

discharge in the form of a short interview and completion

of the above-mentioned scores. As part of the question-

naires, we recorded the presence of side effects and their

severity and impact on rehabilitation.

For this study, full ethical approval was granted from the

local ethics committee as well as full approval from the

Medicines and Healthcare Products Regulatory Agency

(MHRA). Research and Development reference from

Royal Devon and Exeter Hospital: 612163 and Research

Ethics Committee reference: 06/Q2102/57.

Statistical analysis

Based on preliminary data for PCA that we can expect a

15 % reduction in pain worst score after 4 days (which is

what we saw on average), and if there is truly no difference

between the standard and experimental treatment, then 50

patients are required to be 80 % sure that the limits of a

two-sided 90 % confidence interval will exclude a differ-

ence between the standard and experimental group of more

than 30 %.

Continuous outcome data were tested for normality us-

ing the Shapiro Wilks test. If the data were found to be

normally distributed, central tendency was expressed using

means and dispersion using standard deviation. If the data

proved not to be Gaussian, and could not easily be trans-

formed, they were summarised using medians and

1074 Eur J Orthop Surg Traumatol (2015) 25:1073–1079

123

interquartile ranges and comparisons were made using

nonparametric tests such as the Mann–Whitney U test.

Confidence intervals were derived wherever possible.

Categorical data were summarised as proportions and

percentages as appropriate with associated confidence in-

tervals. A comparison of time to discharge was analysed

using Kaplan–Meier survival analysis. Repeated con-

tinuous measures such as VAS pain, OKS, BPI elements

and HADS were analysed using repeated measures analysis

of variance provided the basic requirements were met. The

first 5 days of data were included as in subsequent days,

too many patients had been discharged to make analysis

feasible.

Results

One hundred and ninety-six patients undergoing unilateral

total knee replacement were recruited into the trial. Of

these 64 subsequently withdrew from the trial after initially

consenting and 25 had incomplete data collection for

analysis and were excluded. This left a total of one hundred

and seven patients in the trial with 69 in the LPG, 38 in the

HPG with sixteen of these receiving Fentanyl patches and

lozenges and 22 receiving a PCA infusion (Fig. 1).

The mean age in the LPG was 68; Fentanyl group 64 and

PCA group 66 years. Patient ages ranged from 41 to

96 years with patients in the LPG tending to be older on

average, but this was not statistically significantly different.

Day of discharge

Kaplan–Meier survivorship analysis comparing the three

groups showed a significant difference in day of discharge

between the three groups. Mean time to discharge was

6.23 days for Fentanyl, 5.95 days for PCA and 4.48 days

in the low pain group (p = 0.007) (Fig. 2).

We also analysed the percentage of patients discharged

by day 5. The LPG had the highest rate of discharge

overall, with forty-two (77.8 %) discharged by this time

period. In the HPG, thirteen (68 %) of the PCA group and

7 (5 %) of the Fentanyl group were discharged by day 5;

however, this difference was not significant (p = 0.284).

Pain scores

Pain scores were analysed at day 5 post-operatively as a

large proportion of patients had been discharged after this

time.

Comparison of VAS scores showed that there was no

significant difference in pain scores on movement

(p = 0.317), rest (p = 0.811), worst pain (p = 0.353) and

night (p = 0.730) between the Fentanyl and PCA groups

(see Table 1).

Both HPG groups (Fentanyl and PCA) showed a sig-

nificant reduction, i.e. pain is better, in BPI Worst score,

BPI Average score, BPI Now score, BPI Activity score,

BPI Mood score, BPI Walk score, BPI Relations score, BPI

Work score, BPI Sleep score, BPI Enjoy score (see

Table 2). The reduction in all BPI Worst scores was similar

in both of the treatment groups (i.e. fentanyl from 6.81 to

4.22) and PCA from 7.44 to 4.48). BPI (Now) showed a

significant difference between the LPG and HPG

(p\ 0.001); however, all other modalities of the BPI score showed no significant difference.

Side effects

Using repeated measures ANOVA showed that the side

effect scores between the Fentanyl and PCA groups were

relatively low (1.271–1.417) and did not vary significantly

across the 4 days. There was no significant difference in

side effect score between the two groups, PCA (mean

1.368) and Fentanyl (mean 1.339) (p = 0.887).

Oxford Knee Scores

Both HPG groups (Fentanyl and PCA) demonstrated a

significant reduction in OKS score (p\ 0.001). However, there was no significant difference between the two

treatment groups (p = 0.974) (see Table 3). The reduc-

tion in OKS score was similar in both of the treatment

groups, dropping from a mean of 36.9–28.72 in the

Fentanyl group and 37.16–28.58 in the PCA group (see

Table 3).

Anxiety and depression: HADS scores

Both HPG groups (Fentanyl and PCA) demonstrated a

significant reduction in mean HADS score; 10.16–7.91 in

the Fentanyl group and 12.89–7.06 in the PCA group

(p = 0.004). Comparison of HADS Score for the LPG and

HPG showed no significant difference (p = 0.615).

Discussion

The results from this study show that a post-operative

regime of transdermal Fentanyl patches compares to that of

a more conventional PCA regime in terms of analgesic

effect, day of discharge and side effect profile. By using the

VAS score pre-operatively, we showed that patients can be

allocated into a high or low pain group and consequently a

Eur J Orthop Surg Traumatol (2015) 25:1073–1079 1075

123

targeted analgesic regime can be implemented to suit the

individuals analgesic requirements.

Over the last decade, the emphasis on peri-operative

pain management in joint replacement surgery has made

significant advances, to the extent that many consider it to

be the most substantial advance in clinical practice [8]. A

4-year follow-up study concluded that pain is a common

persistent problem in the community with a relatively high

incidence and low recovery rate [9]. Ip et al. [10] in a

systematic review found that preexisting pain, anxiety, age

and type of surgery are the most significant factors for the

intensity of post-operative pain with type of surgery, age

and psychological distress, the three most important pre-

dictive factors for analgesic consumption.

It is well established that more than half the numbers of

patients undergoing lower limb joint replacement surgery

Assessed for eligibility (n=196)

Excluded (n=90) ♦ Not meeting inclusion criteria (n=26) ♦ Declined to participate (n=64) ♦ Other reasons (n=0)

Analysed (n=14) at day 4 ♦ Excluded from analysis (n=0)

Discontinued intervention (discharged home):- day 1, n=0 day 2, n=0 day 3, n=1 (1) day 4, n=1 (2) day 5, n=1 (3) day 6, n=6 (9) day 7, n=4 (10) (Cumulative totals in brackets)

Allocated to Fentanyl intervention (n=15) ♦ Received allocated intervention (n=15) ♦ Did not receive allocated intervention

(n=0)

Discontinued intervention (discharged home):- day 1, n=0) day 2, n=0) day 3, n=1 (1) day 4, n=3 (4) day 5, n=7 (11) day 6, n=10 (18) day 7, n=0 (18) (Cumulative totals in brackets)

Allocated to PCA intervention (n=23) ♦ Received allocated intervention

(n=23) ♦ Did not receive allocated

intervention (n=0)

Analysed (n=19) at day 4 ♦ Excluded from analysis (n=0)

Allocation

Analysis

Follow-Up

High pain group. Randomized (n=38)

Enrollment

Observational group (low pain) (n=68)

Discontinued intervention (discharged home):- day 1, n=0 day 2, n=0 day 3, n=3 (3) day 4, n=20 (23) day 5, n=27 (50) day 6, n=5 (55) day 7, n=4 (59) (Cumulative totals in brackets)

Analysed (n=45) at day 4 ♦ Excluded from analysis (n=0)

Fig. 1 Consort diagram of study patients

1076 Eur J Orthop Surg Traumatol (2015) 25:1073–1079

123

receive suboptimal analgesia especially during the initial

post-operative period [8], with patients now well informed

to their pain management and consider it a high priority

[2]. However, the importance of delivering adequate

analgesia reaches beyond that of clinical duty with recog-

nition that inadequate pain management can increase the

possibility of developing a poor outcome. Severe post-op-

erative pain results in longer hospital stay, increased opioid

use with resultant side effects and lower patient mood.

Studies have demonstrated that those patients that receive

suboptimal analgesia post-operative have higher levels of

arthrofibrosis and diminished range of motion [5, 11, 12].

In this study, analysis of pre-operative BPI pain score data

demonstrated that theHPGhad a higher percentage of patients

reporting a BPI greater than 5, 61 %, compared to the LPG

which only had 40 %. Early identification of patients likely to

require additional or alternative methods of post-operative

analgesia means maximising rehabilitation enabling

achievement of physiotherapy targets sooner ultimately Fig. 2 Kaplan–Meier curve of discharge days

Table 1 Mean VAS pain scores for pain on movement, at rest, worst and at night. A comparison of fentanyl and PCA interventions in the high pain group and also a comparison of the high pain group with the low pain group

Intervention Mean VAS pain score

Day Pain on movement Pain at rest Worst pain Pain at night

High pain group

Fentanyl

1 7.33 5.83 7.92 8.20

2 7.08 5.25 7.33 5.50

3 5.83 4.17 7.25 4.50

4 5.42 3.50 6.25 4.00

5 5.33 3.50 6.67 3.30

PCA

1 7.67 6.58 8.00 7.71

2 7.67 4.58 8.50 4.43

3 6.75 4.33 7.33 5.00

4 6.08 4.17 7.25 3.86

5 5.50 3.50 6.92 2.71

Within subjects comparison

(i.e. changes over time)

F = 4.9 with 4, 88

df, p = 0.001

F = 5.83 with 4, 88

df, p = 0.001

F = 1.94 with 4, 88

df, p = 0.111

F = 17.83 with 4,

88 df, p = 0.001

Main effect: comparison

of fentanyl versus PCA

F = 1.05 with 1, 22

df, p = 0.317

F = 0.06 with 1, 22

df, p = 0.811

F = 0.90 with 1, 22

df, p = 0.353

F = 0.12 with 1,

22 df, p = 0.730

Low pain group

1 3.06 1.88 3.77 3.46

2 5.00 2.29 5.41 2.85

3 4.88 1.65 5.53 1.85

4 4.88 1.53 5.77 1.77

5 4.47 1.06 5.88 1.69

Within subjects comparison

(i.e. changes over time)

F = 2.17 with 4,

156 df, p = 0.095

F = 6.01 with 4,

156 df, p = 0.001

F = 0.89 with 4,

156 df, p = 0.451

F = 19.97 with 4,

112 df, p\ 0.001 Main effect: comparison

of LPG with HPG

F = 17.87 with 1,

39 df, p\ 0.001 F = 29.39 with 1,

39 df, p\ 0.001 F = 19.87 with 1,

39 df, p\ 0.001 F = 14.54 with 1,

28 df, p = 0.001

Eur J Orthop Surg Traumatol (2015) 25:1073–1079 1077

123

reducing length of stay. In those patients identified as requir-

ing additional analgesic support post-operatively the Fentanyl

transdermal delivery regime has a distinct advantage of pro-

viding a smooth transition to the home environment.

The use of Fentanyl in orthopaedic surgery is limited

with its most common usage being in management of

breakthrough pain in the palliative care setting. Fentanyl

patches do add to the total narcotic dosage as well as

providing an alternative route for administration of anal-

gesia. However, concerns over unpredictable delivery and

the potential for adverse effects does deter many centres

from using Fentanyl through this method. Using Fentanyl

ionophoretic transdermal systems, Viscusi et al. [13, 14]

demonstrated pain control equivalent to standard morphine

PCA delivery systems in a variety of post-operative pa-

tients, with no significant difference in side effect profiles.

Analysis of the side effect profile in our study showed

similar findings with no significant difference demonstrated

between the Fentanyl group and the PCA group.

From this study, we suggest Fentanyl patches and lozenges

provide a viable alternative to the standard morphine based

regime used in most PCA pumps. Fentanyl in a transdermal

therapeutic system provides several attractive features; firstly

it provides stable plasma concentrations in a relatively short

period of time which are maintained a background steady-

state level, secondly newer formulations are safer and bioe-

quivalent to standard oral preparations. Minville et al. re-

ported on a small group of patients who had a fentanyl patch

applied 10 h prior to total hip arthroplasty. No difference in

respiratory depression was noted between that group and

those who did not receive the patch [15, 16]. However, the

use of fentanyl lozenges in this setting is innovative with the

ability of the oral form of Fentanyl to be rapidly absorbed

through the buccal mucosa providing high plasma levels

rapidly means that its profile is ideally suited to managing

breakthrough pain during the post-operative period.

Current trends favour the multimodal approach that

provide adequate analgesia yet minimise opioid-related

Table 2 Mean (and 95 % CI) BPI scores for worst pain and pain now

Intervention BPI worst BPI now

High pain group

Fentanyl

Pre 6.81 (5.74–7.89) 4.90 (3.46–6.34)

Post 4.22 (3.15–5.3) 2.43 (1.30–3.56)

PCA

Pre 7.44 (6.56–8.33) 5.39 (4.2–6.57)

Post 4.48 (3.59–5.37) 2.55 (1.62–3.48)

Within subjects comparison (i.e. change over time) F = 6.74 with 1, 29 df; p = 0.015 F = 3.27 with 1, 29 df; p = 0.081

Main effect: comparison of fentanyl versus PCA F = 0.682 with 1, 29 df; p = 0.486 F = 0.21 with 1, 29 df; p = 0.653

Low pain group

Pre 10.11 (8.35–11.87) 3.56 (2.87–4.25)

Post 6.07 (4.57–7.57) 1.24 (0.8–1.68

Within subjects comparison (i.e. change over time) F = 5.64 with 1, 80 df; p = 0.02 F = 5.38 with 1, 80 df; p = 0.023

Comparison of LPG with HPG F = 2.57 with 1, 80 df; p = 0.113 F = 15.51 with 1, 80 df; p\ 0.001

A comparison of fentanyl and PCA interventions in the high pain group and also a comparison of the high pain group with the low pain group.

Age as a covariate

Table 3 Mean (and 95 % CI) Oxford Knee Score and Hospital Anxiety and Depression Score

Intervention Pre-OKS Post-OKS Pre-HADS Post-HADS

High pain group

Fentanyl 36.9 (32.61–41.19) 28.72 (25.56–31.89) 10.16 (6.38–13.95) 7.91 (5.04–10.79)

PCA 37.16 (33.92–40.41) 28.58 (26.19–30.97) 12.89 (9.77–16.01) 7.06 (4.69–9.43)

Within subjects comparison F = 43.96 with 1, 27 df; p\ 0.001 F = 9.93 with 1, 29 df; p = 0.004 Main effect: comparison of fentanyl versus PCA F = 0.001 with 1, 27 df; p = 0.974 F = 0.26 with 1, 29 df; p = 0.615

Low pain group 35.28 (33.34–39.54) 26.70 (25.03–28.37) 10.11 (8.35–11.87) 6.07 (4.57–7.57)

Within subjects comparison F = 4.78 with 1, 78 df; p = 0.032 F = 5.64 with 1, 79 df; p = 0.02

Comparison of LPG with HPG F = 2.57 with 1, 78 df; p = 0.113 F = 1.42 with 1, 79 df; p = 0.237

A comparison of fentanyl and PCA interventions in the high pain group and also a comparison of the high pain group with the low pain group.

Age as a covariate

1078 Eur J Orthop Surg Traumatol (2015) 25:1073–1079

123

side effects. From this study, we suggest that the use of

Fentanyl in a transdermal delivery system with oral Fen-

tanyl for breakthrough pain provides equivalent pain re-

lieve compared to the more standard opioid based PCA

systems, which several studies have demonstrated provide

adequate cost-efficient pain relief [2, 4]. However, none of

the theoretical advantages were seen as a practical differ-

ence in our patient group. Early identification of patients

falling into the high pain category means that suitable

analgesic regimes can be planned so as to create an envi-

ronment in which both mentally and physically the patient

is able to undertake progressive rehabilitation.

We know that patient expectations correlate highly with

satisfaction and by managing expectations and considering

the mental health of the patient can all help reduce the risk

of overall dissatisfaction. Post-operative pain relief is one

important aspect in the process of undergoing a knee re-

placement with many global factors pertaining to that in-

dividual playing an important role to the overall outcome.

The benefits of splitting patients into low and high pain

groups results means that those patients at risk of devel-

oping severe acute post-operative pain are identified at an

early stage and specific analgesic regime can be imple-

mented so as to manage the pain appropriately in order that

rehabilitation is not compromised. Central to successful

enhanced recovery programs is providing a platform for

patients to mobilise such that they can be discharged safely

with a minimal length of stay. Multi-modal analgesic

regimes we feel are therefore a key component to these

programs. Managing patients post-operative analgesia and

pain perception efficiently can result in faster rehabilitation

and ultimately improved functional outcome and patient

satisfaction. This study demonstrates the potential benefits

of multi-modal analgesia in enabling a faster rehabilitation

in the initial post-operative period and ultimately improves

outcomes.

Conflict of interest None.

References

1. Scott CEH, Howie CR, MacDonald D, Biant LC (2010) Pre-

dicting dissatisfaction following total knee replacement. J Bone

Joint Surg (Br) 92-B:1253–1258

2. Kastanias P, Gowans S, Tumber PS, Snaith K, Robinson S (2010)

Patient-controlled oral analgesia for postoperative pain

management following total knee replacement. Pain Res Manag J

Can Pain Soc 15(1):11–16

3. Werner MU, Mjobo HN, Nielson PR, Rudin A (2010) Prediction

of postoperative pain. A systematic review of predictive ex-

perimental pain studies. Anesthesiology 112:1494–1502

4. Hudova J, McNicol E, Quah C, Lau J, Carr DB (2006) Patient

controlled opioid analgesia versus conventional analgesia for

postoperative pain. Cochrane Database Syst Rev 4:48

5. Singelyn FJ, Deyaert M, Joris D et al (1998) Effects of intra-

venous patient-controlled analgesia with morphine, continuous

epidural analgesia and continuous three-in-one block on postop-

erative pain and knee rehabilitation after unilateral total knee

arthroplasty. Anesth Analg 87:88–92

6. Capdevila X, Barthelet Y, Biboulet P et al (1999) Effects of

perioperative analgesic technique on the surgical outcome and

duration of rehabilitation after major knee surgery. Anesthesi-

ology 91:8–15

7. Collins SL, Faura CC, Moore RA, McQuay HJ (1998) Plasma

concentrations after oral morphine: a systematic review. J Pain

Syndrome Manage 16:388–402

8. Maheshwari AV, Blum YC, Shekhar L, Ranawat A, Ranawat C

(2009) Multimodal pain management after total hip and knee

replacement at the Ranawat Orthopaedic Center. Clin Orthop

Relat Res 467:1418–1423

9. Shipton EA, Tait B (2005) Flagging the pain: preventing the

burden of chronic pain by identifying and treating risk factors in

acute pain -. Eur J Anaesthesiol 22:405–412

10. Ip HYV, Abrishami A, Peng PWH et al (2003) Predictors of

postoperative pain and analgesic consumption. A qualitative

systematic review. Anesthesiology 111:657–677

11. Ranawat CS, Ranawat AS, Mehta A (2003) Total knee arthro-

plasty rehabilitation protocol: what makes the difference?

J Arthroplasty 18(3 Suppl 1):27–30

12. Lundbald H, Kreicbergs A, Jansson KA (2008) Prediction of

persistent pain after total knee replacement for osteoarthritis.

J Bone Joint Surg 90:166–171

13. Viscusi ER, Siccardi M, Damaraju CV, Hewitt DJ, Kershaw P

(2007) The safety and efficacy of fentanyl ionophoretic trans-

dermal system compared with morphine intravenous patient-

controlled analgesia for post-operative pain management: an

analysis of pooled data from three randomized, active-controlled

clinical studies. Pain Med 105(5):1428–1436

14. Viscusi ER, Reynolds L, Chung F, Atkinson LE, Khanna S

(2004) Patient-controlled transdermal fentanyl hydrochloride vs

intravenous morphine pump for postoperative pain. JAMA

291:1333–1341

15. Minville V, Lubrano V, Bounes V et al (2008) Postoperative

analgesia after total hip arthroplasty: patient-controlled analgesia

versus transdermal fentanyl patch. J Clin Anesth 20:280–283

16. Parvizi J, Miller A, Gandhi K (2011) Multimodal pain manage-

ment after total joint arthroplasty. J Bone Joint Surg Am

93:1075–1084

17. Dawson J, Fitzpatrick R, Murray D, Carr A (1998) Questionnaire

on the perception of patients about total knee replacement. J Bone

Joint Surg 80:63–69

Eur J Orthop Surg Traumatol (2015) 25:1073–1079 1079

123

Copyright of European Journal of Orthopaedic Surgery & Traumatology is the property of Springer Science & Business Media B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use.

Our website has a team of professional writers who can help you write any of your homework. They will write your papers from scratch. We also have a team of editors just to make sure all papers are of HIGH QUALITY & PLAGIARISM FREE. To make an Order you only need to click Ask A Question and we will direct you to our Order Page at WriteDemy. Then fill Our Order Form with all your assignment instructions. Select your deadline and pay for your paper. You will get it few hours before your set deadline.