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Reduced medium-term mortality following primary total hip and knee arthroplasty with an enhanced recovery program. A study of 4,500 consecutive procedures.
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PMID:  23368747     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: Our unit started to use routine multimodal techniques to enhance recovery for hip and knee arthroplasty in 2008. We have previously reported earlier discharge, a trend toward a reduction in complications, and a statistically significant reduction in mortality up to 90 days after surgery. In this study, we evaluated the same cohort to determine whether survival benefits were maintained at 2 years.
PATIENTS AND METHODS: We prospectively evaluated 4,500 unselected consecutive total hip and knee replacements. The first 3,000 underwent a traditional protocol (TRAD) and the later 1,500 underwent an enhanced recovery protocol (ER). Mortality data were collected from the Office of National Statistics (UK).
RESULTS: There was a difference in death rate at 2 years (TRAD vs. ER: 3.8% vs. 2.7%; p = 0.05). Survival probability up to 3.7 years post surgery was significantly better in patients who underwent an ER protocol.
INTERPRETATION: This large prospective case series of unselected consecutive patients showed a reduction in mortality rate at 2 years following elective lower-limb hip and knee arthroplasty following the introduction of a multimodal enhanced recovery protocol. This survival benefit supports the routine use of an enhanced recovery program for hip and knee arthroplasty.
Terence Savaridas; Ignacio Serrano-Pedraza; Sameer K Khan; Kate Martin; Ajay Malviya; Mike R Reed
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Publication Detail:
Type:  Journal Article     Date:  2013-01-31
Journal Detail:
Title:  Acta orthopaedica     Volume:  84     ISSN:  1745-3682     ISO Abbreviation:  Acta Orthop     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-15     Completed Date:  2013-04-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101231512     Medline TA:  Acta Orthop     Country:  England    
Other Details:
Languages:  eng     Pagination:  40-3     Citation Subset:  IM    
Northern Deanery Orthopedic Training Programme, UK.
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MeSH Terms
Arthroplasty, Replacement, Hip / mortality,  rehabilitation*
Arthroplasty, Replacement, Knee / mortality,  rehabilitation*
Cause of Death
Great Britain / epidemiology
Kaplan-Meier Estimate
Prospective Studies
Survival Analysis
Treatment Outcome

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Acta Orthop
Journal ID (iso-abbrev): Acta Orthop
Journal ID (publisher-id): ORT
ISSN: 1745-3674
ISSN: 1745-3682
Publisher: Informa Healthcare
Article Information
Copyright: © Nordic Orthopaedic Federation
Received Day: 19 Month: 4 Year: 2012
Accepted Day: 23 Month: 11 Year: 2012
Print publication date: Month: 2 Year: 2013
Electronic publication date: Day: 26 Month: 2 Year: 2013
Volume: 84 Issue: 1
First Page: 40 Last Page: 43
PubMed Id: 23368747
ID: 3584601
DOI: 10.3109/17453674.2013.771298
Publisher Id: ORT_A_771298_O

Reduced medium-term mortality following primary total hip and knee arthroplasty with an enhanced recovery program : A study of 4,500 consecutive procedures
Terence Savaridas1
Ignacio Serrano-Pedraza2
Sameer K Khan3
Kate Martin3
Ajay Malviya3
Mike R Reed3
1Northern Deanery Orthopedic Training Programme, UK
2Complutense University of Madrid, Madrid, Spain
3Northumbria Healthcare NHS Foundation Trust, UK.
Correspondence: Correspondence:

Randomized controlled trials (Reilly et al. 2005, Andersen et al. 2007, Larsen et al. 2008) and clinical series (McDonald et al. 2011) have shown a significant reduction in length of stay in hospital following lower limb arthroplasty with the implementation of enhanced recovery (ER) programs. ER programs are based on the use of multimodal strategies to improve analgesia while at the same time reducing the surgical stress response and organ dysfunction (including nausea, vomiting, and ileus), thus facilitating earlier patient mobilization and return to oral fluids and diet (Kehlet and Wilmore 2008). This enables commencement of functional rehabilitation within the first few hours after surgery (Husted et al. 2011, McDonald et al. 2011). The use of multimodal strategies has resulted in faster patient rehabilitation and improved satisfaction (Kehlet and Wilmore 2002).

Our hospital introduced an ER program for hip and knee arthroplasty in May 2008. We have previously published our findings of statistically significant reductions in length of hospital stay and mortality within 30 days and 90 days of surgery by the use of an ER program compared to our traditional protocol (Malviya et al. 2011). The 90-day mortality of 0.2% in our unit after implementation of an ER program is similar to that previously reported in units with established ER programs (Husted et al. 2010).

Very few results have been published regarding comparison of longer-term mortality after implementation of ER programs in comparison to controls from a cohort of patients whereby multimodal strategies were not used in the perioperative period. A recent study from the United Kingdom found no difference in mortality 1 year after primary total knee arthroplasty following implementation of an ER program in comparison with a historical cohort (McDonald et al. 2011).

We now report on mortality more than 3 years postoperatively following the introduction of an ER program, in comparison to the results of our traditional protocol.

Patients and methods

Data from 4,500 unselected consecutive primary hip and knee replacements were analyzed. 3,000 procedures were performed between March 2, 2004 and May 1, 2008, immediately prior to implementation of the enhanced recovery program (the traditional (TRAD) group); 1,500 procedures were performed with an enhanced recovery program (the enhanced recovery (ER) group) between May 2, 2008 and November 3, 2009. The treating surgeons’ indications for hip and knee arthroplasty remained unchanged. The protocols that were followed in both groups have been published previously (Malviya et al. 2011).

The patients were from a consecutive unselected series. Comparison of patient demographics before surgery in the 2 groups—as previously published (Malviya et al. 2011)—are presented in Table 1. Chi-squared test was used to compare proportions (Fleiss et al. 2003).

Mortality data were obtained from the Office of National Statistics (ONS). In England, deaths must be registered within 5 days. Burials and cremations cannot be conducted without this registration documentation. These deaths are recorded by the ONS and are added to the patient’s health service record. The cause of death for patients that died within our NHS trust was obtained from inspection of hospital case notes, and was cross-referenced with ONS data.


The death rates and cause-of-death data presented for postoperative times up to 2 years include the actual data for all 4,500 patients. There was a greater proportion of patients in the TRAD group with longer follow-up data. The death rates beyond 2 years are therefore only reported using Kaplan-Meier (K-M) survival analysis. K-M survival curves with Greenwood’s 95% confidence interval (CI) were used to assess and compare the survival probability between groups (TRAD and ER). The log-rank test was used to test for any statistically significant difference between the 2 K-M curves (Bland and Altman 2004). Furthermore, the log-rank test was used to determine whether there were any differences in survival, between hip and knee arthroplasty, within each group.


After initiation of the ER program, the mortality rate following primary hip and knee arthroplasty was reduced (p = 0.05) at 2 years (Table 2). With time (up to 3.7 years), the difference in mortality appeared to increase as the K-M survival curves diverged (χ2log-rank = 16, p < 0.001) (Figure 1).

In the ER group, with a sample size that was half that of the TRAD group, it could be expected that the number of deaths at different intervals postoperatively would be half that of the TRAD group. With time, the difference in mortality appeared to increase; there were 12 fewer deaths than expected in the ER group at 1 year and this increased to 17 fewer deaths at 2 years in the ER cohort of 1,500 patients. Although fewer patients in the ER group had 3.7-year follow-up, the projected difference at that point was 5% (75 patients).

From case notes and ONS data, we were unable to ascertain the cause of death of 9 patients in the TRAD group and of 7 patients in the ER group.

The cause of death data (Figure 2) show that at 2 years after surgery, a greater proportion of deaths were related to malignant disease in the TRAD group than in the ER group. Almost half of the patients who died due to malignant disease within 2 years in the ER group (4 of 9) had a known diagnosis of cancer prior to arthroplasty surgery. In the TRAD group, approximately one third of deaths from malignant disease (14 of 36) were in patients who were known to have developed cancer before joint replacement surgery. When K-M survival probability graphs were plotted for both groups after exclusion of all deaths that had been due to malignant disease, there were divergent curves (χ2log-rank = 11, p < 0.001), indicating that a survival benefit remained up to 3.7 years after surgery for patients who underwent an ER protocol.


The ER program is intended to facilitate an early return to function by minimizing stress-induced organ dysfunction after major surgery and its associated morbidity (Kehlet and Wilmore 2002).

Implementation of the ER program appeared to have a positive effect on reducing patient mortality following lower limb arthroplasty; this persisted up to 3.7 years postoperatively. The reason for this prolonged and apparently increasing beneficial effect is not known, but it may relate to the reduced stress response, shorter hospital stay, and improved pain control in the ER program group (Kehlet and Wilmore 2002, McDonald et al. 2011). With the initiation of an ER program in our unit, there was a statistically significant decrease in the postoperative transfusion rate. In contrast, in the TRAD group, there tended to be a greater range of complications—which included return to theater, hospital re-admission, stroke, myocardial infarction, acute renal failure, and thromboembolic events—within the first 2 postoperative months (Malviya et al. 2011). A recent review of prospectively collected multicenter data from over 100,000 patients who had undergone surgical procedures (a proportion of whom had THRs) showed that the occurrence of a postoperative complication within the first 30 days reduced median patient survival at 5 years, independently of patient risk preoperatively (Khuri et al. 2005). The authors suggested that the presence of an inflammatory response related to the postoperative complication may have been a contributory factor to the reduced longer-term survival. Likewise, the reduced 30-day postoperative complication incidence in the ER group in our study may explain the improved longer-term survival. In addition, the stated aim of ER programs—to use multimodal strategies to reduce the surgery-mediated inflammatory stress response (Kehlet and Wilmore 2008)—may in itself contribute to improved longer-term survival.

There has been an increase in detection rates, possibly related to better patient awareness, and there have also been improvements in treatment modalities for the most common malignant diseases in the United Kingdom, namely prostate cancer, breast cancer, colorectal cancer, and lung cancer. The benefits gained from these are evident from the steady increase in 1-year survival rates after diagnosis of a malignant disease over the last 5 years (, accessed Aug 8. 2012). This may partly explain the higher proportion of deaths related to malignant disease in the TRAD group, which was the historical cohort. Furthermore, there is some evidence in the literature to suggest an increase in recurrence of malignant disease after blood transfusion (Blajchman 2005). The rates of malignant disease before surgery in the ER and TRAD groups were similar, but mortality due to malignant disease within 2 years post surgery was greater in the TRAD group. As the ER group had a lower postoperative transfusion rate (Malviya et al. 2011), this may have been a factor in the observed rate of deaths due to malignancy in our study.

The proportion of deaths related to the more commonly encountered post-surgical complications such as stroke, myocardial infarction, cardiac failure, pneumonia, respiratory failure, pulmonary embolism, and renal failure was greater in the TRAD group.

This is the first observational study to specifically assess medium-term mortality in a large number of patients before and after the implementation of an ER program for hip and knee arthroplasty. We found a survival benefit in the longer term following implementation of the ER program. The cause of this survival benefit is still not known, but the present study further supports the routine use of ER programs for hip and knee replacement.

TS collected the data and prepared the manuscript. KM, AM, and SK collected the data and IS-P analyzed them. MRR prepared and implemented the enhanced recovery protocol, and prepared the manuscript.

The authors wish to acknowledge the help of all contributing surgeons, anesthetists, theater practitioners, nursing staff, physiotherapists, occupational therapists, and managers working in the orthopedic service at Northumbria Healthcare NHS Foundation Trust, without whose help and constant support the protocol used in this study could not have been implemented.

No competing interests declared.

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[Figure ID: F1]
Figure 1. 

Kaplan-Meier (K-M) survival curves for both groups ± 95% Greenwood confidence interval (dotted lines). Note that the two K-M survival curves fall outwith the ± 95% Greenwood confidence intervals. The level of significance is 0.05.

[Figure ID: F2]
Figure 2. 

Cause of death for patients who died up to 2 years post surgery, reported as a rate per 1,000 procedures.

[TableWrap ID: T1] Table 1. 

Comparison of patient demographics preoperatively in the 2 groups

(n = 3,000)
(n = 1,500)
p-value a
Mean age, years 69 68
THR 1368 630
TKR 1632 870
Sex (M : F) 1482 : 1518 711 : 789 0.2
Co-morbidities, n (%)
 Hypertension 921 (31) 673 (45) < 0.001
 Atrial fibrillation 143 (5) 84 (6) 0.3
 Ischemic heart disease 211 (7) 113 (8) 0.6
 Diabetes mellitus
 insulin-dependent 20 (0.7) 18 (1) 0.09
 non-insulin-dependent 205 (7) 150 (10) < 0.001
 Chronic obstructive
 pulmonary disease 85 (3) 67 (4) 0.006
 Alzheimer’s disease 6 (0.2) 5 (0.3) 0.6

T1-F1aChi-squared test with continuity correction.

[TableWrap ID: T2] Table 2. 

Comparison of mortality rates in the two groups

(n = 3,000)
(n = 1,500)
(chi-squared test)
Dead by 1 year 63 (2.1%) 19 (1.3%) 0.05
Dead by 2 years 114 (3.8%) 40 (2.7%) 0.05

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