Regional versus general anaesthesia for improved cognitive function after procedures other than cardiac surgery or neurosurgery in adult and paediatric patients.

This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this review is to compare the effects of regional versus general anaesthesia on cognitive function after procedures other than cardiac surgery or neurosurgery in adult and in paediatric patients.

Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety.

OBJECTIVE: To determine the effectiveness and safety of perioperative tranexamic acid use in patients undergoing total hip or knee arthroplasty in the United States. DESIGN: Retrospective cohort study; multilevel multivariable logistic regression models measured the association between tranexamic acid use in the perioperative period and outcomes. SETTING: 510 US hospitals from the claims based Premier Perspective database for 2006-12. PARTICIPANTS: 872,416 patients who had total hip or knee arthroplasty. INTERVENTION: Perioperative intravenous tranexamic acid use by dose categories (none, ≤ 1000 mg, 2000 mg, and ≥ 3000 mg). MAIN OUTCOME MEASURES: Allogeneic or autologous transfusion, thromboembolic complications (pulmonary embolism, deep venous thrombosis), acute renal failure, and combined complications (thromboembolic complications, acute renal failure, cerebrovascular events, myocardial infarction, in-hospital mortality). RESULTS: While comparable regarding average age and comorbidity index, patients receiving tranexamic acid (versus those who did not) showed lower rates of allogeneic or autologous transfusion (7.7% v 20.1%), thromboembolic complications (0.6% v 0.8%), acute renal failure (1.2% v 1.6%), and combined complications (1.9% v 2.6%); all P<0.01. In the multilevel models, tranexamic acid dose categories (versus no tranexamic acid use) were associated with significantly (P<0.001) decreased odds for allogeneic or autologous blood transfusions (odds ratio 0.31 to 0.38 by dose category) and no significantly increased risk for complications: thromboembolic complications (odds ratio 0.85 to 1.02), acute renal failure (0.70 to 1.11), and combined complications (0.75 to 0.98). CONCLUSIONS: Tranexamic acid was effective in reducing the need for blood transfusions while not increasing the risk of complications, including thromboembolic events and renal failure. Thus our data provide incremental evidence of the potential effectiveness and safety of tranexamic acid in patients requiring orthopedic surgery.

Does the impact of the type of anesthesia on outcomes differ by patient age and comorbidity burden?

INTRODUCTION: Neuraxial anesthesia may provide perioperative outcome benefits versus general anesthesia in orthopedic surgical patients. As subgroup analyses are lacking, we evaluated the influence of the type of anesthesia on outcomes in patient groups of different age and the presence of cardiopulmonary disease. METHODS: Data from approximately 500 hospitals in the United States regarding total hip and total knee arthroplasties performed between 2006 and 2012 were accessed. Patients were categorized by age (ie, <65, 65-74, or ≥75 years) as well as the presence of cardiopulmonary disease. Resulting groups were compared with regard to patient, hospital, procedure, and comorbidity-related variables, as well as incidence of major perioperative complications. A multivariable logistic regression analysis was performed to assess the independent influence of the type of anesthesia on complications within each patient subgroup. RESULTS: We identified 795,135 records of patients who underwent total hip arthroplasty or total knee arthroplasty. The incidence of major complications was highest in the oldest patient group with cardiopulmonary disease (26.1%) and the lowest in the youngest group without cardiopulmonary disease (4.5%).Multivariable logistic regressions showed that neuraxial anesthesia was associated with decreased odds for combined major complications, need for intensive care services, and prolonged length of stay compared with general anesthesia in all patient subgroups. For patients without major cardiopulmonary comorbidities, the positive impact of neuraxial anesthesia increased with increasing age. CONCLUSIONS: Neuraxial anesthesia is associated with decreased odds for major complications and resource utilization after joint arthroplasty for all patient groups, irrespective of age and comorbidity burden.

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.

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.

Paraplegia after mastoidectomy under general anesthesia.

We report a case of complete paraplegia after general anesthesia for a right tympanomastoidectomy without any apparent predisposing factors related to the surgical procedure or the anesthetic. The case raises the possibility that the combination of neck rotation and relative hypotension may precipitate paraplegia in patients with preexisting spinal chord pathology.

Calcium chloride prolongs the effects of lidocaine and bupivacaine in rat sciatic nerve.

BACKGROUND AND OBJECTIVES: Elevated extracellular calcium ion has been shown to shift the voltage dependence of Na+- and K+-ion channels rightward, making the nerve less excitable. We hypothesized that calcium chloride (CaCl2) when used as an adjuvant prolongs and intensifies the block by local anesthetics (LAs). We investigated the effects of LAs combined with calcium in rat sciatic nerve blockade and in cultured rat GH3 cells expressing Na+ channels. Furthermore, we tested for histologic changes due to CaCl2. METHODS: We anesthetized rats with sevoflurane, exposed the sciatic nerves, and injected 0.2 mL of 1% lidocaine or 0.1% bupivacaine, alone or coadministered with 0.625%, 1.25%, 2.5%, or 5% CaCl2 (n = 8-10 per group). We assessed the complete-block time and complete-recovery time of proprioception, motor function, and nocifensive reaction. To elucidate the mechanism of nerve block, we performed electrophysiology experiments in cultured rat GH3 cells. Sciatic nerves were harvested at day 7 and stained with hemotoxylin/eosin. RESULTS: The addition of CaCl2 overall prolonged the duration of blockade by lidocaine or bupivacaine. Adding 10 mM CaCl2 to 300 microM lidocaine caused a right shift of the steady-state Na+-channel inactivation curve, indicating that the CaCl2 reduced the potency of lidocaine. Rat sciatic nerves treated with 1% lidocaine coadministered with 5% CaCl2 showed microscopic signs of neurotoxicity. CONCLUSIONS: The mechanism of prolonged nerve block of CaCl2 coadministered with LAs seems to be a raised threshold for nerve excitation. Major histopathologic changes at higher concentrations of CaCl2 are evident, and therefore, clinical application as an adjuvant to LAs seems unlikely.

Coapplication of lidocaine and the permanently charged sodium channel blocker QX-314 produces a long-lasting nociceptive blockade in rodents.

BACKGROUND: Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314-mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia. METHODS: Lidocaine (0.5% [17.5 mM], 1% [35 mM], and 2% [70 mM]) alone, QX-314 (0.2% [5.8 mM]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block. RESULTS: Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block. CONCLUSIONS: Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.

Combined volumetric T1, T2 and secular-T2 quantitative MRI of the brain: age-related global changes (preliminary results).

The combined T1, T2 and secular-T2 pixel frequency distributions of 24 adult human brains were studied in vivo using a technique based on the mixed-TSE pulse sequence, dual-space clustering segmentation and histogram gaussian decomposition. Pixel frequency histograms of whole brains and the four principal brain compartments were studied comparatively and as function of age. For white matter, the position of the T1 peak correlates with age (R2 =.7868) when data are fitted to a quadratic polynomial. For gray matter, a weaker age correlation is found (R2 =.3687). T2 and secular-T2 results are indicative of a weaker correlation with age. The technique and preliminary results presented herein may be useful for characterizing normal as well as abnormal aging of the brain, and also for comparison with the results obtained with alternative quantitative MRI methodologies.