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1.
Adjuvants in clinical regional anesthesia practice: A comprehensive review.
Prabhakar, A, Lambert, T, Kaye, RJ, Gaignard, SM, Ragusa, J, Wheat, S, Moll, V, Cornett, EM, Urman, RD, Kaye, AD
Best practice & research. Clinical anaesthesiology. 2019;(4):415-423
Abstract
Adjuvants are medications that work synergistically with local anesthetics to help enhance the duration and quality of analgesia in regional techniques. Regional anesthesia has become more prevalent as evidence continues to show efficacy, enhancement of patient care, increased patient satisfaction, and improved patient safety. Practitioners in the perioperative setting need to not only be familiar with regional techniques but also the medications used for them. Some examples of adjuvant medications for regional techniques include dexamethasone, alpha 2 agonists such as clonidine and dexmedetomidine, midazolam, buprenorphine, NMDA antagonists, including ketamine and magnesium, neostigmine, sodium bicarbonate, epinephrine, and non-steroidal anti-inflammatory drugs. The aim of the present investigation, therefore, is to provide a comprehensive review of the most commonly used non-opioid adjuvants in clinical practice today. Regional adjuvants can improve patient safety, increase patient satisfaction, and enhance clinical efficacy. Future studies and best practice techniques can facilitate standardization of regional anesthesia adjuvant dosing when providing nerve blocks in clinical practice.
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2.
Effects of anesthetic interventions on breast cancer behavior, cancer-related patient outcomes, and postoperative recovery.
Eden, C, Esses, G, Katz, D, DeMaria, S
Surgical oncology. 2018;(2):266-274
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Abstract
This narrative review will summarize our current understanding of the effects of perioperative interventions on patients undergoing surgical removal of breast malignancies. It will focus on how different anesthetic agents and perioperative interventions might affect both breast cancer behavior and/or tumor recurrence as well as postoperative recovery. The main objective of this study will be to describe the evidence and critically analyze preclinical and clinical studies on the use of intravenous versus inhaled anesthetic agents, opioids, regional anesthetics, and anesthetic adjuncts in patients undergoing breast cancer resection. We will look both at the evidence regarding cancer-related outcomes and postoperative recovery. A search of PubMed, from inception to May 2017 was performed using Mesh terms Breast Neoplasms [Mesh] OR cancer AND breast AND Anesthesia [Mesh]; "Anesthetics"[Mesh] AND "Breast Neoplasms/surgery"[Mesh]. Although no optimal anesthetic combination has been identified for patients undergoing breast cancer resection, it should be noted that based on the available evidence, an ideal anesthetic in this patient population would involve a combination of TIVA (propofol), regional anesthesia (paravertebral block)), non opioid sedatives (clonidine or dexmedetomidine), and COX-2 inhibition (ketorolac). Based on the current evidence, this combination of anesthetic and analgesic agents has the best chance of improving cancer-related outcomes and postoperative recovery.
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3.
Advances in Experimental Medicine and Biology: Intrafascicular Local Anesthetic Injection Damages Peripheral Nerve-Induced Neuropathic Pain.
Tseng, KY, Wang, HC, Chang, LL, Cheng, KI
Advances in experimental medicine and biology. 2018;:65-76
Abstract
Peripheral nerve blockade (PNB) is advantageous for patients undergoing surgery to decrease the perioperative opioid consumptions and enhance recovery after surgery.Inadvertent local anesthetic (LA) administration into nerve fiber intrafascicularly easily results in unrecognized nerve injury. Using nerve block guidance either by ultrasound, electrical nerve stimulator, or using pressure devices does not prevent nerve damage, even though most of the nerve injury is transiently. The incidence of neurologic symptoms or neuropathy is in the range of 0.02-2.2%, and no significant difference of postoperative neurologic symptoms is found as compared with using ultrasound or guided nerve stimulator technique. However, intrafascicular lidocaine brought about macrophage migration into the damaged fascicle, Schwann cell proliferation, increased intensity of myelin basic protein, and shorten withdrawal time to mechanical stimuli. In dorsal root ganglion (DRG), intrafascicular LA injection increased the activated transcriptional factor 3 (ATF-3) and downregulated Nav1.8 (Nav1.8). In spinal dorsal horn (SDH), the microglia and astrocytes located in SDH were activated and proliferated after intrafascicular LA injection and returned to baseline gradually at the end of the month. This is a kind of neuropathic pain, so low injection pressure should be maintained, the correct needle bevel used, nerve stimulator or ultrasound guidance applied, and careful and deliberately slow injection employed as important parts of the injection technique to prevent intrafascicular LA administration-induced neuropathic pain.
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4.
Reversal effects of local anesthetics on P-glycoprotein-mediated cancer multidrug resistance.
Hu, Y, Qin, X, Cao, H, Yu, S, Feng, J
Anti-cancer drugs. 2017;(3):243-249
Abstract
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits. Recent studies have shown that the LAs can interfere with receptors other than the traditional sodium channel. LA can suppress the proliferation of several cancer cells. The inhibition of P-gp could reverse MDR. Interestingly, the LAs, such as lidocaine, can repress ABCB1 (P-gp) expression and reverse MDR. Also, LAs can modulate the tumor necrosis factor/AKT pathway, the tumor necrosis factor/Src pathway, epidermal growth factor receptor, the Wnt pathway, and the RASSF1A/MDM2/p53 pathway to interfere with P-gp function. This means that LAs could be potentially useful in reversing cancer MDR. The aim of this review is to report the nonanesthetic functions of LAs, with a special focus on their anti-MDR effects and their potential beneficial implications in cancer chemotherapy.
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5.
Adjuncts to local anaesthetics in tonsillectomy: a systematic review and meta-analysis.
Vlok, R, Melhuish, TM, Chong, C, Ryan, T, White, LD
Journal of anesthesia. 2017;(4):608-616
Abstract
The infiltration of local anaesthetic agents has been shown to reduce post-tonsillectomy pain. A number of recent studies have shown that the addition of agents such as clonidine and dexamethasone improve the efficacy of nerve blocks and spinal anaesthesia. The aim of this review was to determine whether additives to local anaesthetic agents improve post-tonsillectomy outcomes. Four major databases were systematically searched for all relevant studies published up to August 2016. All study designs with a control group receiving local anaesthetic infiltration and an intervention receiving the same infiltration with an added agent were included in this review. These studies were then assessed for level of evidence and risk of bias. The data were then analysed both qualitatively and where appropriate by meta-analysis. We reviewed 11 randomised controlled trial (RCTs) that included 854 patients. Due to inconsistencies in the methods used to report outcomes, both quantitative and qualitative comparisons were required to analyse the extracted data. Overall, we found that dexamethasone, magnesium, pethidine and tramadol reduce post-operative pain and analgesia use, with dexamethasone in particular significantly reducing post-operative nausea and vomiting and magnesium infiltration significantly reducing the incidence of laryngospasm. This systematic review of RCTs provides strong evidence that the use of dexamethasone and magnesium as additives to local anaesthetics reduces post-tonsillectomy pain and analgesia requirement. There is limited evidence that pethidine and tramadol have a similar effect on pain and analgesia requirement. The studies in this pooled analysis are sufficiently strong to make a level one recommendation that the addition of magnesium to local anaesthetics reduces the incidence of laryngospasm, a potentially lethal post-operative complication. Review level of evidence: 1.
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6.
Epidural therapy for the treatment of severe pre-eclampsia in non labouring women.
Ray, A, Ray, S
The Cochrane database of systematic reviews. 2017;(11):CD009540
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Abstract
BACKGROUND Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required. OBJECTIVES To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour. SEARCH METHODS We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of these, were eligible for inclusion. Trials using a cluster design, and studies published in abstract form only are also eligible for inclusion in this review. Cross-over trials were not eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS The two review authors independently assessed trials for inclusion and trial quality. There were no relevant data available for extraction. MAIN RESULTS We included one small study (involving 24 women). The study was a single-centre randomised trial conducted in Mexico. This study compared a control group who received antihypertensive therapy, anticonvulsant therapy, plasma expanders, corticosteroids and dypyridamole with an intervention group that received epidural block instead of the antihypertensives, as well as all the other four drugs. Lumbar epidural block was given using 0.25% bupivacaine, 10 mg bolus and 5 mg each hour on continuous epidural infusion for six hours. This study was at low risk of bias in three domains but was assessed to be high risk of bias in two domains due to lack of allocation concealment and blinding of women and staff, and unclear for random sequence generation and outcome assessor blinding.The included study did not report on any of this review's important outcomes. Meta-analysis was not possible.For the mother, these were: maternal death (death during pregnancy or up to 42 days after the end of the pregnancy, or death more than 42 days after the end of the pregnancy); development of eclampsia or recurrence of seizures; stroke; any serious morbidity: defined as at least one of stroke, kidney failure, liver failure, HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), disseminated intravascular coagulation, pulmonary oedema.For the baby, these were: death: stillbirths (death in utero at or after 20 weeks' gestation), perinatal deaths (stillbirths plus deaths in the first week of life), death before discharge from the hospital, neonatal deaths (death within the first 28 days after birth), deaths after the first 28 days; preterm birth (defined as the birth before 37 completed weeks' gestation); and side effects of the intervention. Reported outcomesThe included study only reported on a single secondary outcome of interest to this review: the Apgar score of the baby at birth and after five minutes and there was no clear difference between the intervention and control groups.The included study also reported a reduction in maternal diastolic arterial pressure. However, the change in maternal mean arterial pressure and systolic arterial pressure, which were the other reported outcomes of this trial, were not significantly different between the two groups. AUTHORS' CONCLUSIONS Currently, there is insufficient evidence from randomised controlled trials to evaluate the effectiveness, safety or cost of using epidural therapy for treating severe pre-eclampsia in non-labouring women.High-quality randomised controlled trials are needed to evaluate the use of epidural agents as therapy for treatment of severe pre-eclampsia. The rationale for the use of epidural is well-founded. However there is insufficient evidence from randomised controlled trials to show that the effect of epidural translates into improved maternal and fetal outcomes. Thus, there is a need for larger, well-designed studies to come to an evidence-based conclusion as to whether the lowering of vasomotor tone by epidural therapy results in better maternal and fetal outcomes and for how long that could be maintained. Another important question that needs to be answered is how long should extended epidural be used to ensure any potential clinical benefits and what could be the associated side effects and costs. Interactions with other modalities of treatment and women's satisfaction could represent other avenues of research.
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7.
Different interventions in preventing opioid-induced cough: a meta-analysis.
Shuying, L, Ping, L, Juan, N, Dong, L
Journal of clinical anesthesia. 2016;:440-7
Abstract
BACKGROUND Cough is one of the most common complications of opioids. Many studies have evaluated the effect of various drugs in preventing opioid-induced cough (OIC). However, there is existing controversy about those reports. The present study was performed to assess the efficacy of different interventions on OIC. METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Embase to identify randomized controlled trials on the efficacy of different drugs in the prevention of OIC. Opioids included fentanyl, sufentanil, and remifentanil. We mainly investigated the incidence and severity of OIC after different interventions. RESULTS Thirty-four trials including 9906 patients were analyzed in this study. Twenty different drugs were reported, and 10 drugs were indentified in more than 2 articles. These drugs, including lidocaine, ketamine, dexmedetomidine, priming of fentanyl, propofol, dezocine, dexamethasone, dextromethorphan, and magnesium sulfate (MgSO4), showed a significant efficacy compared with controls. There were insufficient numbers of trials for salbutamol, clonidine, tramadol, pentazocine, rocuronium, midazolam, atropine, terbutaline, sodium chromoglycate, beclomethasone, and ephedrine. From these data, we found that salbutamol, tramadol, midazolam, and atropine were ineffective. CONCLUSIONS This meta-analysis suggested that the prophylactic administration of lidocaine, ketamine, dexmedetomidine, priming of fentanyl, propofol, and dezocine was effective in preventing OIC.
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8.
Local Anesthetic-Induced Neurotoxicity.
Verlinde, M, Hollmann, MW, Stevens, MF, Hermanns, H, Werdehausen, R, Lirk, P
International journal of molecular sciences. 2016;(3):339
Abstract
This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor.
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9.
Itch Management: Topical Agents.
Metz, M, Staubach, P
Current problems in dermatology. 2016;:40-5
Abstract
Chronic pruritus is a common problem in patients with inflammatory skin diseases as well as in subjects with dry or sensitive skin. Regardless of the underlying cause of the pruritus, a topical therapy is not only useful but most often necessary to achieve symptom control. A good topical therapy should fulfill different functions. An optimal basic therapy based on the condition of the skin is important to repair epithelial barrier defects and to rehydrate the skin. An adequate disease-specific topical therapy is crucial for inflamed skin, e.g. anti-inflammatory topical therapy is an important part in the treatment of atopic dermatitis. Finally, the use of specific antipruritic substances can help to improve pruritus in patients irrespective of the underlying disease. Here, we summarize topical agents used in the treatment of chronic pruritus.
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10.
Bupivacaine drug-induced liver injury: a case series and brief review of the literature.
Chintamaneni, P, Stevenson, HL, Malik, SM
Journal of clinical anesthesia. 2016;:137-41
Abstract
Bupivacaine is an established and efficacious anesthetic that has become increasingly popular in postoperative pain management. However, there is limited literature regarding the potential for bupivacaine-induced delayed liver toxicity. Describe cholestasis as a potential adverse reaction of bupivacaine infusion into a surgical wound. Retrospective review of patients' medical records. We report the cases of 3 patients with new onset of cholestatic injury after receiving bupivacaine infusion for postoperative herniorrhaphy pain management. All patients had negative serologic workups for other causes of liver injury. All patients achieved eventual resolution of their liver injury. Bupivacaine-induced liver injury should be on the differential of individuals presenting with jaundice and cholestasis within a month of infusion via a surgically placed catheter of this commonly used anesthetic.