Peripheral nerve block anesthesia/analgesia for patients undergoing primary hip and knee arthroplasty: recommendations from the International Consensus on Anesthesia-Related Outcomes after Surgery (ICAROS) group based on a systematic review and meta-analysis of current literature.

BACKGROUND: Evidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery. METHODS: A systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations. RESULTS: Analysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92). CONCLUSIONS: Based on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes. RECOMMENDATION: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Anaesthetic care of patients undergoing primary hip and knee arthroplasty: consensus recommendations from the International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) based on a systematic review and meta-analysis.

BACKGROUND: Evidence-based international expert consensus regarding anaesthetic practice in hip/knee arthroplasty surgery is needed for improved healthcare outcomes. METHODS: The International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) systematic review, including randomised controlled and observational studies comparing neuraxial to general anaesthesia regarding major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, genitourinary, thromboembolic, neurological, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, from 1946 to May 17, 2018 were queried. Meta-analysis and Grading of Recommendations Assessment, Development and Evaluation approach was utilised to assess evidence quality and to develop recommendations. RESULTS: The analysis of 94 studies revealed that neuraxial anaesthesia was associated with lower odds or no difference in virtually all reported complications, except for urinary retention. Excerpt of complications for neuraxial vs general anaesthesia in hip/knee arthroplasty, respectively: mortality odds ratio (OR): 0.67, 95% confidence interval (CI): 0.57-0.80/OR: 0.83, 95% CI: 0.60-1.15; pulmonary OR: 0.65, 95% CI: 0.52-0.80/OR: 0.69, 95% CI: 0.58-0.81; acute renal failure OR: 0.69, 95% CI: 0.59-0.81/OR: 0.73, 95% CI: 0.65-0.82; deep venous thrombosis OR: 0.52, 95% CI: 0.42-0.65/OR: 0.77, 95% CI: 0.64-0.93; infections OR: 0.73, 95% CI: 0.67-0.79/OR: 0.80, 95% CI: 0.76-0.85; and blood transfusion OR: 0.85, 95% CI: 0.82-0.89/OR: 0.84, 95% CI: 0.82-0.87. CONCLUSIONS: Recommendation: primary neuraxial anaesthesia is preferred for knee arthroplasty, given several positive postoperative outcome benefits; evidence level: low, weak recommendation. RECOMMENDATION: neuraxial anaesthesia is recommended for hip arthroplasty given associated outcome benefits; evidence level: moderate-low, strong recommendation. Based on current evidence, the consensus group recommends neuraxial over general anaesthesia for hip/knee arthroplasty. TRIAL REGISTRY NUMBER: PROSPERO CRD42018099935.

Factors associated with hospital admission after rotator cuff repair: the role of peripheral nerve blockade.

STUDY OBJECTIVE: The objective was to analyze the impact of a peripheral nerve block in addition to general anesthesia on hospital admission after surgical rotator cuff repair. DESIGN: This was a population-based outcome study. The cost effectiveness of ambulatory rotator cuff repair relies on the discharge of patients on the day of surgery. As the impact of a peripheral nerve block in addition to general anesthesia on this outcome is unknown, we sought to elucidate this subject using population-based data. PATIENTS AND METHODS: Information on patients undergoing rotator cuff surgery under general anesthesia with or without the addition of a peripheral nerve block (GN vs G) from a retrospective database provided by Premier Perspective, Inc, Charlotte, NC (http://www.premierinc.com), was analyzed. Using multilevel multivariable regressions, we evaluated the independent impact of the type of anesthesia on the outcomes hospital admission, combined major complications, and increased hospital costs. RESULTS: We identified 27,201 patients who underwent surgical rotator cuff repair. Approximately 89% (24,240) of patients were discharged on the day of surgery, whereas 11% (2961) were admitted to the hospital. The admission rates for the GN group were 9.1% and 11.2% for the G group (P=.0001). The multivariable regression models showed that patients with the addition of a peripheral nerve block had 18% less risk of being admitted to the hospital (relative risk [RR]=0.82; 95% confidence interval [CI], 0.74-0.91; P=.0003) compared with those without this intervention. Differences in risk for combined major complications (RR=1.00; 95% CI, 0.83-1.20; P=.9751) or increased hospital costs (RR=0.97; 95% CI, 0.93-1.02; P=.2538) were nonsignificant. DISCUSSION: For patients undergoing surgical rotator cuff repair under general anesthesia, the addition of a peripheral nerve block may be associated with a reduction in the need for postoperative hospital admission after ambulatory surgery. Although the reason for this finding has to remain speculative, better pain control may play a role.

Additives to local anesthetics for peripheral nerve blocks or local anesthesia: a review of the literature.

A multitude of studies have focused on individual additives to local anesthetics and their effect on quality, onset, duration, spread and selectivity, as well as the potential toxic effects of their use. This review aims to give a broad overview of the current evidence in this developing field, based on beneficial and adverse effects of these drugs. We discuss the limitations of the available data and hope to convey implications and future perspectives for clinicians and researchers alike.

Ropivacaine 0.375% vs. 0.75% with prilocaine for intermediate cervical plexus block for carotid endarterectomy: A randomised trial.

BACKGROUND: Carotid endarterectomy is widely performed under regional anaesthesia. Ultrasound guidance is increasingly used in many regional anaesthetic procedures to improve safety and efficacy, and because it can reduce the amount of local anaesthetic required. Despite this, an ideal approach and dosing regimen for cervical plexus block remain elusive. OBJECTIVE: The aim of this study was to compare two different concentrations of ropivacaine in terms of analgesic adequacy, haemodynamic effects and plasma concentration using an ultrasound-guided triple approach for intermediate cervical plexus blockade. DESIGN: A randomised, placebo-controlled, blinded study. SETTING: University Clinic Salzburg, Department of Anaesthesiology, Perioperative Medicine and Intensive Care, Paracelsus Medical University, Salzburg, Austria, from 16 November 2012 to 17 September 2013. PATIENTS: Forty-six patients prospectively randomised to receive ultrasound-guided intermediate cervical block with either 20 ml ropivacaine 0.75% or 20 ml ropivacaine 0.375% each with 20 ml prilocaine 1%. INTERVENTION: After subcutaneous infiltration, blocks were performed using ultrasound-guided infiltration below the sternocleidomastoid muscle, and ultrasound-guided infiltration of the carotid sheath. Ropivacaine and prilocaine plasma concentrations were measured at intervals. MAIN OUTCOME: The primary study endpoint was the volume of supplementary lidocaine 1% required to achieve adequate surgical anaesthesia. Perioperative haemodynamic variables and pain scores were recorded. RESULTS: There was no statistical difference in the volume of supplementary lidocaine given: 5.0 (±3.63) ml in the ropivacaine 0.375% group and 5.17 (±2.76) ml in the ropivacaine 0.75% group (P = 0.846). Pain scores were similarly low across both groups. Measured concentrations of ropivacaine and prilocaine did not reach toxic levels in either group. Levels of ropivacaine were approximately two-fold higher in the 0.75% group [mean area under the curve (AUC) 10 531.11 (±2912.84) vs. 5264.34 ng (±1594.69), P < 0.0001]. Perioperative cardiovascular stability was excellent in both groups. There were no serious block-related complications. CONCLUSION: An ultrasound-guided intermediate block provides adequate anaesthesia for carotid thrombendarterectomy with a little need for supplementary local anaesthetic. Use of 0.375% ropivacaine provided similarly effective analgesia as 0.75%, but resulted in significantly lower plasma concentrations. TRIAL REGISTRATION: The study was registered at the European Clinical Trial Database (Eudra CT No.: 2012-002769) as well as at ClinicalTrials.gov (NCT01759940).

Utility of intraoperative lung ultrasonography.

A patient with an endobronchial tumor and critical airway obstruction developed hypoxia and hypercarbia and, subsequently, cardiac arrest during a palliative laser core-out excision. The differential diagnosis included tension pneumothorax, as well as airway obstruction due to swelling of residual tumor or to blood clots. In this case, empiric needle decompression could have had deleterious consequences. Immediate bedside lung ultrasonography provided real-time information leading to the stabilization of the patient. This case provides compelling motivation for anesthesiologists to acquire this easily learned skill.

Dexmedetomidine added to ropivacaine extends the duration of interscalene brachial plexus blocks for elective shoulder surgery when compared with ropivacaine alone: a single-center, prospective, triple-blind, randomized controlled trial.

BACKGROUND AND OBJECTIVES: Research suggests that the addition of dexmedetomidine to local anesthetics can prolong peripheral nerve blocks; however, clinical safety data are limited, and interscalene blocks have not been studied. The present study was designed to test the hypothesis that dexmedetomidine added to ropivacaine would safely enhance the duration of analgesia without adverse effects when compared with ropivacaine alone. METHODS: We conducted a single-center, prospective, randomized, triple-blind, controlled trial of 62 patients undergoing elective shoulder surgery under general anesthesia with an interscalene block. Patients underwent ultrasound-guided interscalene blocks using either 12 mL of 0.5% ropivacaine or 0.5% ropivacaine plus 150-µg dexmedetomidine. The primary outcomes were self-reported duration of the nerve block and safety assessment (adverse effects and neurological sequelae). Data were analyzed in a blinded fashion. RESULTS: The median duration of the nerve block was 18 hours (95% confidence interval, 18-20) in the dexmedetomidine group and 14 hours (95% confidence interval, 14-16) in the ropivacaine group (P = 0.0001). Dexmedetomidine also lowered pain scores for the first 14 hours postoperatively and significantly hastened the time to sensory (P = 0.04) and motor (P = 0.002) block onset. Dexmedetomidine lowered heart rate but blood pressures were stable. Plasma levels of ropivacaine were not different between groups, and plasma dexmedetomidine levels were relatively low. There were no adverse events or neurological sequelae. CONCLUSIONS: Dexmedetomidine added to ropivacaine for interscalene blocks increased the duration of the nerve block and improved postoperative pain. These additional efficacy and safety data should encourage further study of peripheral perineural dexmedetomidine in humans.

Ephedrine shows synergistic motor blockade when combined with bupivacaine or lidocaine for spinal anesthesia in a rat model.

BACKGROUND: Ephedrine is a direct/indirect vasoactive drug. In addition, it also possesses intrinsic local anesthetic properties, mainly due to its sodium-channel blockage. We investigated whether ephedrine demonstrates a synergistic effect with bupivacaine and lidocaine when injected via a spinal catheter into the spinal space of rats. METHODS: Spinal catheters were surgically placed in 47 rats (n = 8 per group; 7 rats were excluded.) Bupivacaine, lidocaine, and ephedrine in various concentrations and constant volumes (60 µL) were injected into the spinal catheters to determine the equipotency of each drug. Ephedrine in combination with either bupivacaine or lidocaine was then injected into the spinal catheters. RESULTS: Ephedrine demonstrated statistically significant synergistic effects with bupivacaine as well as with lidocaine in fixed combinations. The combination index reflecting a synergistic effect was 0.792 (95% confidence interval: 0.665-0.919) for ephedrine + bupivacaine and 0.663 (95% confidence interval: 0.532-0.794) for ephedrine + lidocaine. CONCLUSION: Ephedrine combined with either bupivacaine or lidocaine acted synergistically to block motor function and has the potential to reduce the amount of local anesthetic needed for spinal block. The synergistic effect of ephedrine in combination with local anesthetics is an interesting pharmacological phenomenon that warrants further clinical evaluation.

Local anesthetic-induced inhibition of human neutrophil priming: the influence of structure, lipophilicity, and charge.

BACKGROUND AND OBJECTIVES: Local anesthetics (LAs) are widely known for inhibition of voltage-gated sodium channels underlying their antiarrhythmic and antinociceptive effects. However, LAs have significant immunomodulatory properties and were shown to affect human neutrophil functions independent of sodium-channel blockade. Previous studies suggest a highly selective interaction between LAs and the α-subunit of G protein-coupled receptors of the Gq/G11 family as underlying mechanism. Providing a detailed structure function analysis, this study aimed to determine the active parts within the LA molecule responsible for the effects on human neutrophil priming. METHODS: Human neutrophils were incubated with structurally different LAs for 60 minutes, followed by priming and activation using either platelet-activating factor or lysophosphatidic acid and N-formyl-methionyl-L-leucyl-L-phenylalanine. Superoxide anion generation was determined, using the cytochrome c reduction assay. RESULTS: Differences in priming inhibition of human neutrophils between LAs were smaller than expected, although significant. Ester-linked LAs blocked priming responses more effectively than did amide LAs. Furthermore, the inhibitory potency of LAs on priming decreased with an increase of their respective octanol-buffer coefficient, and inhibition did not correlate with sodium-channel-blocking potency. Charge was not crucially required for priming inhibition, yet it played a role in effect size. CONCLUSIONS: Local anesthetics significantly attenuated Gαq-protein-mediated neutrophil priming. The most potent inhibition was achieved by ester compounds, inversely correlated with their octanol-buffer coefficient, and enhanced by permanent charges within the LA molecule. No correlation to their potency of blocking sodium channels was found.

Demographics and perioperative outcome in patients with depression and anxiety undergoing total joint arthroplasty: a population-based study.

BACKGROUND: Depression and anxiety are highly prevalent psychiatric disorders. However, little is known about their impact on outcomes in the perioperative setting. This study is intended to gain insight into epidemiology and effects on perioperative morbidity, mortality, length of hospital stay, discharge and cost. METHODS: We obtained the National Inpatient Sample from the Hospital Cost and Utilization Project for each year between 2000 and 2008. Entries indicating the performance of primary total hip and knee arthroplasty were identified and separated into four groups: (1) those with concomitant diagnosis of depression or (2) anxiety, (3) both, and (4) none of these diagnoses. The incidence of major complications, non-routine discharge, length, and cost of hospitalization were assessed. Regression analysis was performed to identify if psychiatric comorbidity was an independent risk factor for each outcome. RESULTS: We identified 1,212,493 patients undergoing arthroplasty between 2000 and 2008. The prevalence of depression and anxiety significantly increased over time. Patients with either condition had higher hospital charges, rates of non-routine discharges and comorbidity index. Depression or anxiety were associated with significantly decreased adjusted odds for in-hospital mortality (OR = 0.53, p = 0.0147; OR = 0.58, p = 0.0064). The risk of developing a major complication was slightly lower in patients with depression, anxiety or both (OR=0.95, p = 0.0738; OR = 0.95, p = 0.0259; OR = 0.94, p = 0.7349). CONCLUSIONS: Patients suffering from depression, anxiety, or both require more healthcare resources in a perioperative setting. However, lower short-term mortality in spite of higher comorbidity burden and without extensive changes in perioperative complication profile indicates better outcome for this group of patients.

The Qualitative Hyperalgesia Profile: A New Metric to Assess Chronic Post-Thoracotomy Pain.

Thoracotomy often results in chronic pain, characterized by resting pain and elevated mechano-sensitivity. This paper defines complex behavioral responses to tactile stimulation in rats after thoracotomy, shown to be reversibly relieved by systemic morphine, in order to develop a novel qualitative "pain" score. A deep incision and 1 hour of rib retraction in male Sprague-Dawley rats resulted in reduced threshold and a change in the locus of greatest tactile (von Frey filament) sensitivity, from the lower back to a more rostral location around the wound site, and extending bilaterally. The fraction of rats showing nocifensive responses to mild stimulation (10 gm) increased after thoracotomy (from a pre-operative value of 0/10 to 8/10 at 10 days post-op), and the average threshold decreased correspondingly, from 15 gm to ∼4 gm. The nature of the nocifensive responses to tactile stimulation, composed pre-operatively only of no response (Grade 0) or brief contractions of the local subcutaneous muscles (Grade I), changed markedly after thoracotomy, with the appearance of new behaviors including a brisk lateral "escape" movement and/or a 180° rotation of the trunk (both included as Grade II), and whole body shuddering, and scratching and squealing (Grade III). Systemic morphine (2.5 mg/kg, i.p.) transiently raised the threshold for response and reduced the frequency of Grade II and III responses, supporting the interpretation that these represent pain. The findings support the development of a Qualitative Hyperalgesic Profile to assess the complex behavior that indicates a central integration of hyperalgesia.

Comparative perioperative outcomes associated with neuraxial versus general anesthesia for simultaneous bilateral total knee arthroplasty.

BACKGROUND AND OBJECTIVES: The influence of the type of anesthesia on perioperative outcomes after bilateral total knee arthroplasty (BTKA) remains unknown. Therefore, we examined a large sample of BTKA recipients, hypothesizing that neuraxial anesthesia would favorably impact on outcomes. METHODS: We identified patient entries indicating elective BTKA between 2006 and 2010 in a national database; subgrouped them by type of anesthesia: general (G), neuraxial (N), or combined neuraxial-general (NG); and analyzed differences in demographics and perioperative outcomes. RESULTS: Of 15,687 identified procedures, 6.8% (n = 1066) were performed under N, 80.1% (n = 12,567) under G, and 13.1% (n = 2054) under NG. Comparing N to G and NG, patients in group N were, on average, younger (63.9, 64.6, and 64.8 years; P = 0.030) but did not differ in overall comorbidity burden. Patients in group N required blood product transfusions significantly less frequently (28.5%, 44.7%, 38.0%; P < 0.0001). In-hospital mortality, 30-day mortality, and complication rates tended to be lower in group N, without reaching statistical significance. After adjusting for covariates, N and NG were associated with 16.0% and 6.0% reduction in major complications compared with G, but only the reduced odds for the requirement of blood transfusions associated with N reached statistical significance (N vs G: odds ratio, 0.52 [95% CI, 0.45-0.61], P < 0.0001; NG vs G: odds ratio, 0.77 [95% CI, 0.69-0.86], P < 0.0001). CONCLUSIONS: Neuraxial anesthesia for BTKA is associated with significantly lower rates of blood transfusions and, by trend, decreased morbidity. Although by itself the effect may be limited, N might be used within a multimodal approach to reduce complications after BTKA.

In Zucker diabetic fatty rats, subclinical diabetic neuropathy increases in vivo lidocaine block duration but not in vitro neurotoxicity.

BACKGROUND AND OBJECTIVES: Application of local anesthetics may lead to nerve damage. Increasing evidence suggests that risk of neurotoxicity is higher in patients with diabetic peripheral neuropathy. In addition, block duration may be prolonged in neuropathy. We sought to investigate neurotoxicity in vitro and block duration in vivo in a genetic animal model of diabetes mellitus type 2. METHODS: In the first experiments, neurons harvested from control Zucker diabetic fatty (ZDF) rats were exposed to acute (24 hours) or chronic (72 hours) hyperglycemia, followed by incubation with lidocaine 40 mM (approximately 1%). In a second experiment, neurons harvested from control ZDF rats, or diabetic ZDF rats, were incubated with lidocaine, with or without SB203580, an inhibitor of the p38 mitogen-activated protein kinase. Finally, we performed sciatic nerve block (lidocaine 2%, 0.2 mL) in control or diabetic ZDF rats and measured motor and nociceptive block duration. RESULTS: In vitro, neither acute nor chronic hyperglycemia altered neurotoxic properties of lidocaine. In vitro, incubation of neurons with lidocaine resulted in a slightly decreased survival ratio when neurons were harvested from diabetic (57% ± 19%) as compared with control (64% ± 9%) rats. The addition of SB203580 partly reversed this enhanced neurotoxic effect and raised survival to 71% ± 12% in diabetic neurons and 66% ± 9% in control rats, respectively. In vivo, even though no difference was detected at baseline testing, motor block was significantly prolonged in diabetic as compared with control rats (137 ± 16 vs 86 ± 17 min). CONCLUSIONS: In vitro, local anesthetic neurotoxicity was more pronounced on neurons from diabetic animals, but the survival difference was small. In vivo, subclinical neuropathy leads to substantial prolongation of block duration. We conclude that early diabetic neuropathy increases block duration, whereas the observed increase in toxicity was small.

Trends in in-hospital major morbidity and mortality after total joint arthroplasty: United States 1998-2008.

BACKGROUND: The use of total joint arthroplasties is increasing worldwide. In this work we aim to elucidate recent trends in demographics and perioperative outcomes of patients undergoing total hip (THA) or total knee arthroplasty (TKA). METHODS: Data from the US Nationwide Impatient Sample between 1998 and 2008 were gathered for primary THAs and TKAs. Trends in patient age, comorbidity burden, length of hospitalization, frequency of major perioperative complications, and in-hospital mortality were analyzed. In-hospital outcomes were reported as events per 1000 inpatient days to account for changes in length of hospitalization over time. Deyo index, discharge status, and the interaction effect of time and discharge status were included in the adjusted trend analysis for morbidity. RESULTS: Between 1998 and 2008, the average age of patients undergoing TKA and THA decreased by 2 to 3 years (P < 0.001). The average length of stay decreased by approximately 1 day over the time interval studied (P < 0.001). The percentage of patients being discharged home declined from 29.7% to 25.4% after TKA and from 29.3% to 24.2% after THA, in favor of dispositions to long- and short-term care facilities (P < 0.0001). Comorbidity burden as measured by the Deyo comorbidity index increased by 35% and 30% for TKA and THA patients, respectively (P < 0.0001). After TKA, there was an increase in the incidence of the following major complications: pulmonary embolism (coefficient estimate [CE] 0.069; 95% confidence interval [CI], 0.059-0.079; P < 0.0001), sepsis (CE 0.034; 95% CI, 0.014-0.054; P = 0.001), nonmyocardial infarction cardiac complications (CE 0.038; 95% CI, 0.035-0.041; P < 0.0001), and pneumonia (CE 0.039; 95% CI, 0.031-0.047; P < 0.0001). After THA, there was an increase in the incidence of the following major complications: pulmonary embolism (CE 0.031; 95% CI, 0.012-0.049; P = 0.001), sepsis (CE 0.060; 95% CI, 0.039-0.081; P < 0.0001), nonmyocardial infarction cardiac complications (CE 0.040; 95% CI, 0.036-0.043; P < 0.0001), and pneumonia (CE 0.039; 95% CI, 0.029-0.048). In-hospital mortality declined after both TKA (CE -0.059; 95% CI, -0.077 to -0.040; P < 0.0001) and THA (CE -0.068; 95% CI, -0.086 to -0.051; P < 0.0001). CONCLUSION: Between 1998 and 2008, trends show increases in several major in-hospital complications after THA and TKA, including pulmonary embolism, sepsis, nonmyocardial infarction cardiac complications, and pneumonia. Despite the increase in complications, declining in-hospital mortality was noted over this period.

Epidemiology and risk factors for perioperative mortality after total hip and knee arthroplasty.

The perioperative mortality of total knee and hip arthroplasties (TKA, THA) remains a major concern among health care providers and their patients. The increase in utilization of TKA and THA makes it imperative to be aware of factors that are associated with this unfortunate event. Therefore we analyzed the Nationwide Inpatient Sample data from 1998 to 2008 and compared admissions with perioperative mortality to those that survived their hospitalization. An estimated total of 4,438,213 TKA and 2,182,121 THA procedures were performed in the United States between 1998 and 2008. The average mortality rate for TKA was 0.13% and 0.18% for THA, or 0.34 and 0.44 events per 1,000 inpatient days, respectively. Independent risk factors for in-hospital mortality were advanced age, male gender, ethnic minority background, emergency admission as well as a number of comorbidities and complications. Furthermore, we demonstrated that the timing of death occurred earlier after TKA when compared to THA, with 50% of fatalities occurring by day 4 versus day 6 of the hospitalization, respectively. This study provides nationally representative information on risk factors for and timing of perioperative mortality after TKA and THA. Our data can be used to assess the risk for perioperative mortality and to develop targeted intervention to decrease such risk.

Perioperative management of partial face transplantation involving a heparin antibody-positive donor.

Heparin-induced thrombocytopenia (HIT) is an immunologic condition that may lead to thrombosis. We present a case of face transplantation from a donor who had suffered a severe stroke, possibly from HIT, during cardiac surgery. The procedure was planned to include full heparinization. The anesthesia team was involved in the early planning phase and had detailed access to the donor's medical history; alternative anticoagulation for the donor and recipient was suggested so as to avoid a possible complication.

Prolonged cutaneous analgesia with transdermal application of amitriptyline and capsaicin.

BACKGROUND AND OBJECTIVES: Capsaicin selectively binds to TRPV1, the vanilloid subtype 1 of the superfamily of transient receptor potential ion channels, which is highly expressed in pain-transmitting C fibers. Recent reports have demonstrated that the coadministration of capsaicin with a local anesthetic (LA) at the rat sciatic nerve elicits a prolonged nociceptive-selective nerve block, suggesting that activation of the TRPV1 receptor may allow LAs to enter the nerve through the TRPV1 pore. In previous studies, we demonstrated that transdermal amitriptyline achieves clinical analgesic effects and is more potent than lidocaine. Here we examine whether the combined application of amitriptyline and capsaicin as a transdermal patch will produce prolonged cutaneous analgesia compared with amitriptyline alone. METHODS: Male Sprague-Dawley rats (weights 250-300 g) were assigned to five treatment groups (n = 6-8 per group). Transdermal patches containing amitriptyline with different concentrations of capsaicin were applied for 3 hrs to rats' shaved backs: 2.5% amitriptyline alone (control group) and in combination with 0.05%, 0.15%, 1%, and 8% capsaicin. Behavioral testing for cutaneous nociception was conducted before drug application and after patch removal using the cutaneous trunci muscle reflex. In addition, skin appearance was assessed to determine irritation by these formulations. RESULTS: The cutaneous analgesic effect is significantly prolonged when amitriptyline is applied in combination with 8% capsaicin. Amitriptyline alone provided a complete block to pinprick for 4.5 hrs, and the time to full recovery was 96 hrs. Amitriptyline with 8% capsaicin produced a complete block to pinprick for 6 to 9 hrs, and the time to full recovery was 216 hrs (P = 0.002). Amitriptyline alone causes toxic effects in skin, whereas the higher the concentration of capsaicin, the less skin irritation was noted, and the combination of amitriptyline 2.5% with capsaicin 8% caused no adverse skin reactions. CONCLUSIONS: This study demonstrates that the combined application of amitriptyline and capsaicin results in prolonged cutaneous analgesia compared with amitriptyline alone, suggesting that the activation of the TRPV1 channel by capsaicin facilitates the passage of amitriptyline into nociceptors. This transdermal patch achieves far longer cutaneous analgesia than currently available patch applications such as EMLA cream. The mechanism that underlies the lesser skin irritation noted when amitriptyline is combined with higher doses of capsaicin compared with amitriptyline alone is unclear and may be related to a counteraction of amitriptyline-induced vasoconstriction.

Prolonged suppression of postincisional pain by a slow-release formulation of lidocaine.

BACKGROUND: Postoperative pain can occur despite nerve blocks during the surgical period. Here we tested Xybrex (Orthocon, Inc., Irvington, NY), a slow-release formulation of lidocaine that blocks rat sciatic nerve for 1-2 days, for its ability to suppress postincisional pain. METHODS: A plantar paw incision was made in rats, either along the midline (Brennan model) or at the lateral edge, 30 min after different treatment groups received either lidocaine (0.2 ml, 2%) or Xybrex implant at the ipsilateral sciatic nerve or Xybrex at the contralateral sciatic nerve. Behavioral testing by von Frey filaments occurred at 2 and 6 h postoperatively and for the next 10 postoperative days. The fractional response (paw withdrawal responses per 10 pokes) was scored at each time. RESULTS: Mechanosensitivity from the Brennan paw incision was reduced throughout the postoperative period by ipsilateral Xybrex, although lidocaine injection almost had no effect. Contralateral Xybrex had a weaker but still significant antihyperalgesic effect, converging to that from ipsilateral Xybrex at postoperative day 2. Xybrex at the nuchal midline reduced allodynia for only postoperative days 1-3, whereas hyperalgesia was reduced continuously after postoperative day 2. Hyperalgesia from the lateral incision was also reduced by ipsilateral Xybrex but not by contralateral Xybrex. CONCLUSIONS: Implants of slow-release lidocaine formulations are most effective against postincisional pain when placed at the ipsilateral nerve innervating the area of incision. Contralateral nerve implants are somewhat less effective, probably acting by releasing lidocaine into the systemic circulation. There appears to be a differential role of central sensitization between postincisional allodynia and hyperalgesia.

The relationship between functional sciatic nerve block duration and the rate of release of lidocaine from a controlled-release matrix.

BACKGROUND: Nerve blocks of long duration are often desirable in perioperative and postoperative situations. The relationship between the duration of such blocks and the rate at which a local anesthetic is released is important to know for developing a localized drug delivery system that will optimize block duration. METHODS: Lidocaine concentration was varied in 1 series of formulations (OSB-L) containing a constant amount of release rate modifier. In another series (OST-R), the release rate modifier was varied while the lidocaine content was held constant. Release kinetics were measured in vitro and correlated to the in vivo duration of antinociceptive and motor block effects when the formulation was implanted next to the rat sciatic nerve. In parallel studies, rats receiving different formulations of slow-release lidocaine were fixed by intracardiac perfusion with 4% paraformaldehyde and nerve-muscle tissue taken for histopathological analysis. RESULTS: In this study, we have demonstrated that the most important variable for effecting functional nerve block, i.e., the blockade of impulses in the relevant fibers of the sciatic nerve, is the rate of lidocaine release at that time. For the OSB-L formulations (lidocaine concentrations of 1.875%, 3.75%, 7.5%, and 15% at a constant release rate modifier of 5%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 0.91 +/- 0.28 and 1.75 +/- 0.61 mg/h, respectively. For the OST-R formulations (16% lidocaine with release rate modifier concentrations of 1.875%, 3.75%, 7.5%, and 15%), the average in vitro release rates at 50% recovery of motor block and nociceptive block were 2.33 +/- 1.39 and 4.34 +/- 1.09 mg/h, respectively. The OSB-L formulations showed a dose-dependent increase in block duration proportional to an increase in initial lidocaine concentration, whereas the OST-R formulations showed a nonmonotonic relationship between release rate modifier concentration and block duration. The histopathological studies at 24 hours, 3, 5, or 7 days, and 4 weeks after the implantation revealed inflammatory reactions with degrees correlated with lidocaine content, but limited to the connective tissue and muscle immediately surrounding the implanted material. Despite these observed inflammatory reactions, nociceptive and motor block function returned to normal, preimplantation values in all animals. CONCLUSIONS: Increasing initial lidocaine content proportionately increased the duration of functional sciatic nerve block. However, decreasing the release rate per se does not give a proportional increase in block duration. Instead, there seems to be an optimal, intermediate release rate for achieving the maximum duration of block.

Resiniferatoxin combined with antidepressants preferentially prolongs sensory/nociceptive block in rat sciatic nerve.

BACKGROUND: Current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. Recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block. METHODS: Rats were anesthetized with isoflurane, and 0.2 mL of amitriptyline, doxepin, or fluoxetine was deposited next to the surgically exposed sciatic nerves (n = 8 per group). Some animals received a second injection containing RTX (n = 8 per group). The effect of nerve block was assessed by neurobehavioral tests of the motor function (extensor postural thrust) and the nocifensive reaction (mechanical pinch). RESULTS: A single application of RTX produced nociceptive-selective sciatic nerve block, whereas antidepressants produced nociceptive and motor block. The combined administration of RTX and antidepressant resulted in a predominantly nociceptive nerve block. Compared with antidepressants or RTX alone, the combination prolonged the nociceptive nerve block more than the motor block. CONCLUSIONS: The combined application of RTX and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. However, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. The mechanisms through which RTX affects nociceptive signal transduction/transmission have yet to be fully elucidated.