Use of preoperative opioids increases duration of hospital stay following elective lower limb arthroplasty. - A snapshot of UK practice

Abstract

This study is one of the first in the UK where to assess the link between pre-operative opioid use and length of stay or complications. The primary objective was to test our hypothesis; that low dose pre-operative opioids will not lead to an increase in complications and LOS in lower limb arthroplasty patients. 640 records were found and 625 patients were included whom received elective primary or revision surgery. It was found that Pre-operative opioids >12 MED does increase LOS.

1. Introduction

Opioids are amongst the most commonly prescribed drugs for musculoskeletal pain. They are the drug of choice for chronic pain and can be found in all pain management protocols.¹ Opioids play an essential role in the non-operative and perioperative management pathways of arthritis and arthroplasty surgery. They are the analgesic option after paracetamol and topical NSAIDs for the management of knee arthritis.² Opioids are known to cause constipation, nausea, dry mouth, sedation and decrease respiratory drive.^3,4 There is no strong evidence for the benefit of long-term opioids, even if they demonstrate short term benefit.^5,6 Opioid dependence is the commonest cause of drug related death in the USA. The number of overdose-associated deaths with prescription opioids was higher than those associated with heroin in 2017.⁷ Opioids are the commonest drugs used in controlling post-operative pain.

There has been a lot of research into the use of opioids in orthopaedics. Most of these studies were conducted in North America where 80% of global prescribed opioids are consumed by less than 5% of the global population.⁸ The National Treatment Agency (NTA) for substance misuse in England issued a report of addiction to prescription and over the counter medicines in 2011, where they found a 5-fold increase in the number opioid items being prescribed between 1991 and 2009.⁹ This indicated the need for further research into opioid prescribing practices in the UK.

This study is one of the first in the UK that assesses the link between pre-operative opioid use and length of stay (LOS) or complications.

The primary objective is to test our hypothesis; that low dose pre-operative opioids will not lead to an increase in complications and LOS in lower limb arthroplasty patients. Secondary objectives include the assessment of other analgesics used, physiotherapy (PT) and intra-articular (IA) injections in the sample.

2. Methods

The NHS is a public health care system, and this makes calculating costs more difficult in comparison to North American systems. However, looking at complications, which are costly and increase in LOS we can assess the impact and cost-effectiveness of pre-operative opioids on our elective orthopaedic services.

The dose of pre-operative opioids being used by patients was investigated and separated into two groups. The first group comprised of patients receiving 12.5 mg morphine equivalent dose (MED) or less. This included all over-the-counter opioid medicines and any weaker opioids being used. Patients receiving more than 12.5 mg MED were allocated to the second group, which included synthetic opioids, opioids in patch form, as well as opioids used for breakthrough pain.

Records of all patients who received elective lower limb arthroplasty surgery in our academic unit in 2016 and 2017 were examined by the 2 main investigators. 640 records were found and 625 patients were included whom received elective primary or revision surgery. The patients underwent one of 6 main procedures; total knee replacement, partial knee replacement, revision knee replacement, total hip replacement, hip resurfacing and revision hip replacements. They were performed by 2 fellowship trained orthopaedic surgeons. 15 patients were excluded from the study as their records were missing or they were admitted as an emergency.

No ethical approval was required as there was no direct patient contact. All GP referral letters and inpatient records were retrospectively examined for opioid prescribing and demographics. LOS and complications were assessed in the discharge letters. Other data collected included PT, IA injections, NSAID use, Paracetamol use and other pain generating conditions (OPGC).

2.1. Opioid use

The type and dose of opioids were collected in the sample. This included Codeine, Dihydrocodeine, Co-Codamol, Tramadol, Morphine, Methadone, Oramorph, Oxycontin, Oxynorm, and Buprenorphine and Fentanyl patches.

2.2. LOS

Patients are planned to be discharged within 5 post-operative days. Patients are discharged when they are medically fit and deemed safe on crutches.

2.3. Complications

All post-operative complications were included. They were divided into procedure specific, opioid specific or others.

All patients are admitted on the day of surgery and all followed the same clinical protocol. The posterior approach is used for all hip surgeries and the medial parapatellar is used for all knee surgeries, they are extended as necessary for revision surgery. Cefuroxime is given on induction for all primary surgery as per protocol. The only exception being patient that are allergic or are receiving a revision who receive Teicoplanin and Gentamicin. All patients receive low molecular weight heparin and TED stockings for DVT prophylaxis. Tranexamic acid is given to all patients. Patients receive physiotherapy sessions and are seen by occupational therapy daily from the first post-operative day. Opioid are heavily relied upon for post-operative pain. Patients are discharged if they are deemed functionally fit with no surgical concerns. Patients are usually discharged with Dihydrocodeine for pain relief. Patients in both groups were matched for co-morbidities and ASA grade.

3. Analysis

A Regression and Kruskal-Wallis analyses was performed to look for the association between pre-operative opioid usage and complications or LOS on IBM SPSS version 21 on Mac.

4. Results

The sample was 58.9% (368) females and 41.1% (257) males with a mean age 70.5 years ranging from 23 to 92. The mean LOS was 4 days ranging from 1 to 133. There were 50 complications (8%).

Our sample included 625 elective procedures consisting of 31.4% (196) total knee replacements, 62.6% (391) total hip replacements, 1.1%⁷ Revision knee replacements, 1.3%⁸ Revision hip replacements, 3% (19) Partial Knee replacements and 0.6%⁴ hip resurfacing.

48% (304) of the sample had OPGC, which included other joint arthritis, RA, polymyalgia rheumatica and other conditions. NSAID use was 47% (299) in the sample while 6% (38) had clear contra-indications for its use. 50.9% (318) of the sample received PT and 51.4% (321) had an IA injection.

4.1. Opioids

Pre-operative opioids were used by 34.4% (214) of the sample. Oral opioids made up the majority with a few cases of transdermal patches. Codeine with paracetamol ‘CO-CODAMOL’ (35mg/500 mg) was the most prescribed agent. The majority of the group taking CO-CODAMOL, were on 12 mg MED or less. Pre-operative opioid patients were further split into two groups which consisted of 20.3% (127) patients on a dose of <12 MED and 12.9% (87) patients on a dose of >12 MED. Patients who were using over the counter opioids were included in the <12 MED group. The non-opioid group was also split into two groups of which 61.3% (383) were not prescribed opioids and 4.5% (28) were allergic to opioids.

4.2. LOS

A Kruskal-Wallis H test was run to look at the difference in the LOS between patients according to their opioid use: ‘>12 MED’ (n = 87), ‘<12 MED’ (n = 127), ‘None’ (n = 383) and ‘Allergy’ (n = 28) (Fig. 1). (see Table 1)

Fig. 1.

Kruskal - Wallis test.

Table 1.

Length of stay in hospital.

Opioids	Mean	N
>12 MED	4.747	87
None	3.238	383
<12 MED	4.157	127
Total	4.04	597

Visually inspecting the boxplot revealed the distributions to be similar between groups (Fig. 1).

Median length of hospital stay scores were statistically significantly different between the patient groups χ²³ = 10.220, p = .017 (Fig. 2).

Fig. 2.

Pairwise comparison of Narcotics.

Subsequently Pairwise comparisons were performed using Dunn's (1964) procedure with a Bonferroni correction for multiple comparisons (see Table 2). Adjusted p-values are presented. This post hoc analysis revealed statistically significant differences in median length of hospital stay scores between the no opioids group ‘None’ (6.24) and the ‘>12 MED’ opioids (6.75) (p = .031), but not between any other group combination (Table 3).

Table 2.

Hypothesis test summary.

Null Hypothesis	Test	Significance	Decision
The distribution of length of stay is the same across categories of Narcotics	Independent Samples Krusal Wallis Test	0.017	Reject the Null Hypothesis

Table 3.

Pairwise Comparison of Narcotic doses.

Sample 1 – Sample 2	Test Statistic	Std Error	Std Test Statistic	Sig	Adj Sig
None - <12 MED	−34.160	18.238	−1.873	0.061	.366
None – Allergy	−44.970	34.869	−1.290	.197	1.000
None - > 12MED	59.109	21.154	2.794	.005	.031
<12 MED – Allergy	10.809	37.186	.291	.771	1.000
<12 MED - >12 MED	24.949	24.788	1.006	.314	1.000
Allergy - >12 MED	14.140	38.700	.365	.715	1.000

4.3. Complications

There were 50 reported complications in our sample, which accounts for (8%). These were divided into three distinct groups; Opioid related, Procedure specific, and other. There were 10 knee specific complications, 6 were post-operative stiffness requiring manipulation under anaesthetic. There were 9 hip specific complications, 33% were haematoma requiring drainage. There were 7 opioid related complications; 15% confusion and 85% ileus which was the commonest. There were 24 other complications and hospital acquired pneumonia (HAP) was the commonest at 58% (Table 4).

Table 4.

Complications.

Complication	Numbers
Total Knee Replacement
Knee Stiffness	6
Infection	1
SSSI	1
DVT	1
Fat Embolism	1
Hip
Total Hip Replacement
Dislocation	2
Superficial Infection	2
Haematoma	3
DVT	1
Loosening	1
Opioid related
Ileus	6
Confusion	1
OTHER
HAP	14
UTI	3
Sepsis	2
Anaemia	2
Thrombocytopenia	1
MI	1
Prolonged recovery	1

A complications binomial logistic regression was performed to ascertain the effects of age, gender, procedure and opioids on the likelihood that participants have complications. Linearity of the continuous variable with respect to the logit of the dependent variable was assessed via the Box-Tidwell (1962) procedure. A Bonferroni correction was applied using all fifteen terms in the model resulting in statistical significance being accepted when p < .00333 (Tabachnick & Fidell, 2014). Based on this assessment, all continuous independent variables were found to be linearly related to the logit of the dependent variable. There were forty-three standardized residuals with a value > ±2 standard deviations, which were kept in the analysis. The logistic regression model was statistically not significant, χ²¹¹ = 15.063, p = .180. The model explained 5.6% (Nagelkerke R²) of the variance in complications and correctly classified 92.0% of cases. Sensitivity, specificity, positive predictive value and negative predictive value were unreliable. No association was found between opioids and complications in our sample.

5. Discussion

34% of the sample were pre-operative opioid users this is similar to North American samples as shown by Riddle et al. 31% and Zarling et al. 34%.^10,11 Opioids are generally prescribed by the primary care physician or pain team in the UK, whilst patients in America tend to get multiple prescriptions from different medical specialist and 24% of those are prescribed by the orthopaedic surgeon.¹⁰

No dose test analyses were found in the literature with regards to opioid usage in arthroplasty surgery. None of the published studies looked into MED or divided samples according to dose. As opioids form such a cornerstone in pain management protocols it is important to see if a smaller dose can be given to patients while reducing risks. The results obtained from the analysis show that a pre-operative opioid dose of >12 MED increases LOS in comparison to non-users. 10 et al. and 11 et al. have shown in their samples that opioids increased LOS and complications in arthroplasty and spinal surgery. The results can be used as a platform for further prospective trials and dose test analyses of opioids in arthroplasty.

No link has been found between complications and pre-operative opioids in our sample. This can be attributable to our low complication rate and small sample size.

6. Limitations

The retrospective nature of the study and the small sample are the major limitations of the study. It is difficult to assess if patients have actually been using their prescribed opioids. Other causes which are also known to increase LOS, like BMI and sociodemographic status,¹² were not collected.

7. Conclusion

Pre-operative opioids >12 MED does increase LOS as shown in the analysis. Therefore, general practitioners and orthopaedic surgeons should try and minimise or avoid opioid based drugs whilst managing pain in the pre-operative period. Further prospective studies in this area could reveal the true economical and rehabilatative impact of opioids in patients underoing lower limb arthroplasty procedures. Strategies to analyse the risk of overuse and overdose before prescribing opioids is recommended.