Pain Management with Early Regional Anesthesia in Geriatric Hip Fracture Patients.

BACKGROUND: Geriatric hip fracture patients are susceptible to the adverse effects of opioid-induced analgesia. Fascia iliaca blocks (FIBs) have emerged as an analgesic technique for this population. There are limited data on a preoperative FIB's effect on perioperative opioid intake. We hypothesized that preoperative FIB would reduce perioperative opioid consumption, measured in morphine milliequivalents (MMEs). DESIGN: This is a prospective observational study. SETTING: A level 1 trauma center in California. PARTICIPANTS: From March 2017 to December 2017, patients 65 years and older presenting with a hip fracture received a preoperative FIB and were prospectively observed. This cohort was compared with a historical control. INTERVENTION: All prospectively enrolled patients were given FIBs. For a single-shot FIB, a 30- to 40-mL bolus of 0.25% bupivacaine with 1:200,000 epinephrine was injected. For a continuous FIB, a bolus of 10 to 20 mL of 0.2% bupivacaine was injected, followed by a continuous infusion of 0.2% bupivacaine at 6 mL/h ending on the morning of postoperative Day 1. RESULTS: A total of 725 patients were included in this study, with 92 in the prospectively collected cohort. The mean age of this cohort was 84.2 (standard deviation = 8.4) years, and 69.2% were female. Patients who received a preoperative FIB consumed less MME preoperatively, 18.0 (interquartile range = 6.0-44.5) versus 29.5 (interquartile range = 6.0-56.5) (P = .007), with no change in pain scores. No differences were found in postoperative opioid consumption between groups. There was no difference in MME or pain score in patients with dementia. Subgroup analysis based on fracture pattern (femoral neck and intertrochanteric) demonstrated a significant decrease in preoperative MME consumption in femoral neck fractures only, 12.0 (interquartile range = 5.0-24.0) versus 29.0 (interquartile range = 12.0-59.0) (P < .001). CONCLUSION: FIBs reduce preoperative opioid intake and have low rates of opioid-related adverse events in geriatric hip fracture patients. LEVEL OF EVIDENCE: The level of evidence was II.

A Comparison in Outcomes of Preoperative Single-shot versus Continuous Catheter Fascia Iliaca Regional Anesthesia in Geriatric Hip Fracture Patients.

BACKGROUND: Fascia iliaca nerve blocks relieve pain in geriatric hip fracture patients and can be administered via a single-shot or continuous catheter. We compared perioperative opioid consumption and pain scores between these two blocks. METHODS: We performed a prospective, observational cohort study, including geriatric hip fracture patients who received a preoperative block. We compared morphine milligram equivalent (MME) consumption and visual analog scale (VAS) pain scores between single-shot and continuous fascia iliaca blocks at multiple time points: preoperative and on postoperative (POD) day 0, 1, and 2. We compared the change in preoperative total and hourly opioid consumption before and after block placement within and between groups. Secondary outcomes included opioid related adverse events, length of stay, and readmission rates. RESULTS: 107 patients were analyzed, 66 received a single-shot and 41 a continuous block. No significant differences were found between both blocks at any time point for median MME consumption or pain scores. MME [IQR]: preoperative 20.5 [6.0,48.8] vs. 24.0 [8.8,48.0], p=0.95; POD0 6.0 [0.0,18.6] vs. 10.0 [0.0,14.0], p=0.52; POD1 12.0 [0.0,30.0] vs. 18.0 [5.0,24.0], p=0.69; POD2 6.0 [0.0,21.2] vs. 12.0 [0.0,24.0], p=0.54. VAS [IQR]: preoperative 4.0 [2.2,5.3] vs. 4.6 [3.2,5.3], p=0.34; POD0 1.3 [0.0,3.7] vs. 2.5 [0.0,3.6], p=0.73; POD1 2.9 [1.7,4.4] vs. 3.7 [1.5,4.7], p=0.59; POD2 2.4 [1.0,4.4] vs. 3.3 [1.9,4.2], p=0.18. Preoperative MME/hr significantly decreased after the block for both groups: 1.05 [0.0,2.2] to 0.0 [0.0,0.0], p < 0.001; 1.4 [0.6,3.1] to 0.0 [0.0,0.1], p < 0.001. The reduction in MME/hr between groups was not significantly different: 0.9 [0.0,1.9] vs. 1.4 [0.6,3.1], p = 0.067. We found no significant differences in secondary outcomes between groups. CONCLUSIONS: We report no differences in opioid use and pain scores between single-shot and continuous catheter fascia iliaca nerve blocks. Both blocks similarly reduce preoperative opioid consumption.

Time to Block: Early Regional Anesthesia Improves Pain Control in Geriatric Hip Fractures.

BACKGROUND: Fascia iliaca nerve blocks (FIBs) anesthetize the thigh and provide opioid-sparing analgesia for geriatric patients with hip fracture awaiting a surgical procedure. FIBs are recommended for preoperative pain management; yet, block administration is often delayed for hours after admission, and delays in pain management lead to worse outcomes. Our objective was to determine whether opioid consumption and pain following a hip fracture are affected by the time to block (TTB). We also examined length of stay and opioid-related adverse events. METHODS: This prospective cohort study included patients who were ≥60 years of age, presented with a hip fracture, and received a preoperative FIB from March 2017 to December 2017. Individualized care timelines, including the date and time of admission, block placement, and surgical procedure, were created to evaluate the effect that TTB and time to surgery (TTS) had on outcomes. Patterns among TTB, TTS, and morphine milligram equivalents (MME) were investigated using the Spearman rho correlation. For descriptive purposes, we divided patients into 2 groups based on the median TTB. Multivariable regression for preoperative MME and length of stay was performed to assess the effect of TTB. RESULTS: There were 107 patients, with a mean age of 83.3 years, who received a preoperative FIB. The median TTB was 8.5 hours. Seventy-two percent of preoperative MME consumption occurred before block placement (pre-block MME). A longer TTB was most strongly correlated with pre-block MME (rho = 0.54; p < 0.001), and TTS was not correlated. Patients with a faster TTB consumed fewer opioids preoperatively (12.0 compared with 33.1 MME; p = 0.015), had lower visual analog scale scores for pain on postoperative day 1 (2.8 compared with 3.5 points; p = 0.046), and were discharged earlier (4.0 compared with 5.5 days; p = 0.039). There were no differences in preoperative pain scores, postoperative opioid consumption, delirium, or opioid-related adverse events. Multivariate regression showed that every hour of delay in TTB was associated with a 2.8% increase in preoperative MME and a 1.0% increase in the length of stay. CONCLUSIONS: Faster TTB in geriatric patients with hip fracture may reduce opioid use, pain, and length of stay. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Brain selective transgene expression in zebrafish using an NRSE derived motif.

Transgenic technologies enable the manipulation and observation of circuits controlling behavior by permitting expression of genetically encoded reporter genes in neurons. Frequently though, neuronal expression is accompanied by transgene expression in non-neuronal tissues, which may preclude key experimental manipulations, including assessment of the contribution of neurons to behavior by ablation. To better restrict transgene expression to the nervous system in zebrafish larvae, we have used DNA sequences derived from the neuron-restrictive silencing element (NRSE). We find that one such sequence, REx2, when used in conjunction with several basal promoters, robustly suppresses transgene expression in non-neuronal tissues. Both in transient transgenic experiments and in stable enhancer trap lines, suppression is achieved without compromising expression within the nervous system. Furthermore, in REx2 enhancer trap lines non-neuronal expression can be de-repressed by knocking down expression of the NRSE binding protein RE1-silencing transcription factor (Rest). In one line, we show that the resulting pattern of reporter gene expression coincides with that of the adjacent endogenous gene, hapln3. We demonstrate that three common basal promoters are susceptible to the effects of the REx2 element, suggesting that this method may be useful for confining expression from many other promoters to the nervous system. This technique enables neural specific targeting of reporter genes and thus will facilitate the use of transgenic methods to manipulate circuit function in freely behaving larvae.

The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model.

OBJECTIVE: The cryopyrinopathies are a group of rare autoinflammatory disorders that are caused by mutations in CIAS1, encoding the cryopyrin protein. However, cryopyrin mutations are found only in 50% of patients with clinically diagnosed cryopyrinopathies. This study was undertaken to investigate the structural effect of disease-causing mutations on cryopyrin, in order to gain better understanding of the impact of disease-associated mutations on protein function. METHODS: We tested for CIAS1 mutations in 22 patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome, 12 with Muckle-Wells syndrome (MWS), 18 with familial cold-induced autoinflammatory syndrome (FCAS), and 3 probands with MWS/FCAS. In a subset of mutation-negative patients, we screened for mutations in proteins that are either homologous to cryopyrin or involved in the caspase 1/interleukin-1beta signaling pathway. CIAS1 and other candidate genes were sequenced, models of cryopyrin domains were constructed using structurally homologous proteins as templates, and disease-causing mutations were mapped. RESULTS: Forty patients were mutation positive, and 7 novel mutations, V262A, C259W, L264F, V351L, F443L, F523C, and Y563N, were found in 9 patients. No mutations in any candidate genes were identified. Most mutations mapped to an inner surface of the hexameric ring in the cryopyrin model, consistent with the hypothesis that the mutations disrupt a closed form of cryopyrin, thus potentiating inflammasome assembly. Disease-causing mutations correlated with disease severity only for a subset of known mutations. CONCLUSION: Our modeling provides insight into potential molecular mechanisms by which cryopyrin mutations can inappropriately activate an inflammatory response. A significant number of patients who are clinically diagnosed as having cryopyrinopathies do not have identifiable disease-associated mutations.