Editor’s Perspective
• Many observational analyses and ongoing randomized trials have evaluated the potential value of neuraxial versus general anesthesia for hip fracture surgery

• The association between peripheral nerve blocks and outcomes after hip fracture surgery is less well studied

• Among elderly patients undergoing emergency hip fracture surgery in Ontario, Canada, peripheral nerve blocks may be associated with slightly decreased postoperative lengths of stay and health system costs

• The use of peripheral nerve blocks was not associated with a difference in postoperative pneumonia rates

Background

Adverse outcomes and resource use rates are high after hip fracture surgery. Peripheral nerve blocks could improve outcomes through enhanced analgesia and decreased opioid related adverse events. We hypothesized that these benefits would translate into decreased resource use (length of stay [primary outcome] and costs), and better clinical outcomes (pneumonia and mortality).

Methods

The authors conducted a retrospective cohort study of hip fracture surgery patients in Ontario, Canada (2011 to 2015) using linked health administrative data. Multilevel regression, instrumental variable, and propensity scores were used to determine the association of nerve blocks with resource use and outcomes.

Results

Table 3.

### Post Hoc Sensitivity Analyses

In the analysis limited to people who were discharged alive from hospital, the adjusted ratio of means for length of stay was 0.95 (95% CI, 0.92 to 0.98). In the analysis that included anesthesia type as a categorical variable, the adjusted ratio of means from the regression model was 0.96 (95% CI, 0.93 to 0.99); when this categorical anesthesia type was used in the IV analysis, the peripheral nerve block–attributable decrease in length of stay was estimated to be 1.0 day (95% CI, 0.9 to 1.2). When the hospital identifier was entered into our primary adjusted regression model as a categorical fixed effect, the ratio of means was 0.97 (95% CI, 0.95 to 0.99). There was no significant adjusted difference in the odds of institutional discharge between people with and without a peripheral nerve block (odds ratio, 0.97; 95% CI, 0.89 to 1.09).

In this population-based cohort of older people having emergency hip fracture surgery, the receipt of a peripheral nerve block was associated with a small decrease in length of postoperative hospital stay (that was statistically significant, but of questionable clinical significance) and decreased health system costs (approximately 5% lower). These findings were consistent across a variety of analytic approaches, including instrumental variable and propensity score analyses and are consistent with the positive effects of peripheral nerve blocks previously described in a systematic review of small randomized trials.18  Given the increasing number of older people in Western populations, these findings are promising, however, the effect sizes varied notably (largest upper confidence limit, 1.2 days; smallest lower confidence limit, 0.2 days). This suggests that future multicenter randomized trials are likely required to provide more definitive causal data and should include patient-centered outcomes.

Hip fractures are the most common surgical indication for hospitalization in older people, and although rates of hip fracture are decreasing, the aging of the population means that hip fractures will continue to be a major driver of emergency healthcare utilization by older adults.1,2,45  Additionally, the comorbidity burden of older people who experience a hip fracture is increasing,2  leaving many hip fracture patients vulnerable to the adverse effects of systemic analgesic therapies.15,16  A recent Cochrane review found that peripheral nerve blocks may offer advantages in hip fracture patients, with high quality evidence supporting a clinically relevant decrease in pain on movement immediately after block placement (–3.4 on a 10-point scale), and moderate evidence of decreased time to first mobilization (11 h shorter), reduced rates of pneumonia (relative risk, 0.41), and lower analgesic costs.18  However, despite the large number of hip fracture surgeries that occur each year, findings from the Guay et al.’s Cochrane review were limited; most were small and single center and few reported key outcomes. For example, only three studies (total n = 131) evaluated pneumonia, and only two studies (total n = 155) evaluated time to mobilization.

Findings from our study build on Guay et al.’s Cochrane review, as the beneficial patient-level impacts of peripheral nerve blocks identified in randomized trials appear to translate into beneficial health system outcomes at a population level, including more than 7,000 potential hospital days saved per year if applied across 13,000 surgeries annually. Causally, improved pain control and earlier ambulation could translate into earlier discharge readiness and decreased healthcare resource use. The potential causality (i.e., internal validity) of our findings are further supported by the minimal differences in patient characteristics between individuals who received a peripheral nerve block and those who did not, as well as by the consistency of the directional effect across three different analytic approaches, including an instrumental variable analysis (which may address issues of unmeasured confounding more effectively than traditional methods in observational research46,47 ). The fact that effect sizes differed between each approach likely reflects the slightly different question addressed by each analysis.34,48,49  Our primary approach (i.e., regression analysis) provides an estimate of average treatment effect; in other words, what would happen if the entire population received a peripheral nerve block compared to no one receiving a nerve block. In contrast, the instrumental variable analysis provides a local average treatment effect estimate (i.e., what is the treatment effect in people who were eligible and willing to have or not have a peripheral nerve block). In this case, this local average treatment effect cannot be extrapolated to the types of patients who would never receive a peripheral nerve block (such as someone with an absolute contraindication or totally unwilling to have a peripheral nerve block), or someone who would almost always receive a peripheral nerve block. However, in the setting of a peripheral nerve block for hip fracture surgery the local average treatment effect may be practice- and policy-relevant as very few absolute contraindications to peripheral nerve blocks exist, and few patients would always be expected to receive a peripheral nerve block. Finally, the propensity score matched analysis provides an estimate of the average effect of treatment in the treated, which reflects the impact of a peripheral nerve block in the subset of the population who actually received a block. The positive impact of peripheral nerve blocks was also reflected in an estimated reduction in health system costs of greater than $1,400 CAD per patient. Considering that more than 13,000 hip fractures per year are treated surgically on Ontario, these savings could translate into more than$18 million dollars in yearly health system savings.

The inconsistency between our findings related to pneumonia (no decrease in the odds of pneumonia after receipt of a peripheral nerve block) and systematic review findings (decreased pneumonia risk with a peripheral nerve block) must also be considered and could reflect numerous issues. First, across the three trials included in the Cochrane review, only 25 pneumonias were identified.50–52  A single study drove results with a control group respiratory infection rate of 43%.50  Therefore, these findings may be fragile.53  Furthermore, these three trials were conducted between 1980 and 2003, and may not reflect contemporary practice. Finally, although the pneumonia definition used has been validated,26  misclassification bias is always a risk in observational research. Whether the causal pathway involves other postulated benefits of peripheral nerve blocks, such as early mobilization or reduced incidence of delirium, these outcomes cannot be accurately captured in administrative data. Specifically, functional data are not routinely captured and diagnostic codes for delirium suffer from substantial misclassification bias.54,55  Therefore, prospective multicenter trials are needed to address patient-centered outcomes and to elucidate specific causal pathways.

### Strengths and Limitations

Our findings should be considered in the context of the study’s strengths and limitations. First, as an observational study, we could only estimate an association (as opposed to causation) between peripheral nerve blocks and outcomes. We also used health administrative data that were not initially collected for research purposes and are therefore at risk of misclassification bias. However, our exposure and outcome variables have been validated and demonstrate a high level of accuracy relative to clinical data. We were not able to capture outcomes considered as typical opioid-related adverse events (e.g., nausea, pruritis, respiratory depression), therefore our findings provide no insights into how peripheral nerve blocks impact these relatively common clinical outcomes. We did not capture postdischarge opioid use either. Our adjusted analyses included a large set of measurable postulated confounding variables, accounted for clustering at the hospital level, and had consistent results across analytic approaches. Furthermore, while observational research is at risk of unmeasured confounding, our instrumental variable analysis (which can help to account for unmeasured confounders) estimated a larger treatment effect than our regression-based analysis. We were unable to account for exactly what type of peripheral nerve block was placed (e.g., fascia iliac vs. femoral), how successful each peripheral nerve block placement was in establishing effective analgesia, or whether adjuncts (such as local anesthesia additives or additional analgesics like intrathecal opioids) were provided; therefore, our effect estimates reflect a pragmatic (as opposed to explanatory) research question.56  We also limited our analyses to perioperative blocks (within 1 day of surgery); therefore, the role of blocks placed on arrival in the emergency department were not captured. We must also acknowledge that small differences in length of stay may not be as relevant at the individual patient level as at the health system level. Finally, the external validity of these results beyond Ontario will require confirmation in future research.

### Conclusions

In a population-based cohort study of older people having emergency hip fracture surgery, receipt of a peripheral nerve block was consistently associated with reduced postoperative length of stay and reduced health system costs. These findings suggest that peripheral nerve blocks could contribute to improved population-level health system outcomes for hip fracture surgery patients. An appropriately powered multicenter trial will be required to estimate a causal relationship with patient-centered outcomes.

### Research Support

Drs. McIsaac, Lalu, and Abdallah receive salary support from The Ottawa Hospital Department of Anesthesiology and Pain Medicine (Ottawa, Ontario, Canada). Dr. McIsaac is supported by the Canadian Anesthesiologists’ Society (Toronto, Ontario, Canada) Career Scientist Award. This study was also supported by ICES (Toronto, Ontario, Canada), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (Toronto, Ontario, Canada). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred. These data sets were held securely in a linked, de-identified form and analyzed at the Institute for Clinical Evaluative Sciences. This study used The Johns Hopkins Adjusted Clinical Groups System, version 10.

### Competing Interests

The authors declare no competing interests.

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