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.

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.

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.

The effects of resiniferatoxin in an experimental rat thoracotomy model.

BACKGROUND: Chronic pain after thoracotomy has been reproduced in a rat model that allows investigation of drugs that might reduce the incidence of allodynia after thoracotomy. Previous studies suggest that morphine, clonidine, neostigmine, gabapentin, and bupivacaine reduce the incidence of allodynia in the rat postthoracotomy pain model. One purpose of this study was to test whether intercostal injection of resiniferatoxin (RTX) decreased the amount of allodynia in an animal model of chronic postthoracotomy pain. We also tested whether RTX induced a transient mechanical hyperalgesic response in uninjured animals. METHODS: Male Sprague-Dawley rats were anesthetized, and the right fourth and fifth ribs were surgically exposed. The pleura was opened, and the ribs were retracted. Intercostal RTX 0.8 or 8 microg was injected in animals that developed allodynia after surgery; a control group underwent rib retraction and received vehicle only. An additional group of uninjured animals received RTX. Rats were tested for mechanical allodynia at a predetermined area around the incision site for 3 wk. RESULTS: Allodynia developed in 42% of the animals that underwent thoracotomy. A transient hyperalgesic response was noted in the uninjured group that underwent drug injections. Intercostal RTX did not modify the course of allodynia in injured rats. DISCUSSION: The current results suggest that intercostal RTX causes a transient hyperalgesic response in uninjured animals and is ineffective in reducing the mechanical allodynia after thoracotomy.

Low-dose systemic bupivacaine prevents the development of allodynia after thoracotomy in rats.

BACKGROUND: Chronic pain after thoracotomy has been recently reproduced in a rat model that allows investigation of the effect of drugs that might reduce the incidence of allodynia after thoracotomy. Previous studies suggest that intrathecal or systemic morphine, clonidine, neostigmine, and gabapentin reduce the incidence of allodynia in the rat postthoracotomy pain model. Our purpose was to test whether intercostal and systemic injection of bupivacaine prevented the development of allodynia in an animal model of chronic intercostal neuropathic pain. METHODS: Male Sprague-Dawley rats were anesthetized and the right 4th and 5th ribs surgically exposed. The pleura were opened and the ribs were retracted for 1 h. Intercostal or systemic bupivacaine 1 mg (0.2 mL at 0.5%) was injected before and after surgery, or before surgery; a control group underwent rib retraction and did not receive any drug. Rats were tested for mechanical allodynia at a predetermined area around the incision site during the 3 wk after surgery. RESULTS: Allodynia developed in 43% of the animals that did not receive bupivacaine (control group); in contrast, allodynia developed in only 6%, 12%, and 12% of those animals that received intercostal bupivacaine before surgery, after surgery, or systemically before surgery, respectively. DISCUSSION: Previous studies suggest that allodynia after rib retraction can be prevented by opioids, alpha2-adrenergic agonists, neostigmine, and gabapentin. The current results suggest that bupivacaine is effective in preventing mechanical allodynia, whether given by intercostal injection before or after surgery, or systemically before surgery.

Postthoracotomy pain management problems.

Pain after thoracotomy is very severe, probably the most severe pain experienced after surgery. Thoracic epidural analgesia has greatly improved the pain experience and its consequences and has been considered the standard for pain management after thoracotomy. This view has been challenged recently by the use of paravertebral nerve blocks. Nevertheless, severe ipsilateral shoulder pain and the prevention of the postthoracotomy pain syndrome remain the most important challenges for management of postthoracotomy pain.

Safety evaluation of topically applied amitriptyline in porcine full-thickness wounds.

BACKGROUND AND OBJECTIVES: The tricyclic antidepressant amitriptyline is frequently used in pain clinics for management of pain. It has also been suggested that topical application of amitriptyline could be useful for the treatment of neuropathic pain. In this report we investigated the effect of amitriptyline on porcine full thickness wounds resembling excised burn wounds. We assessed if daily topical application of amitriptyline into the wound chambers for 10 days impedes wound healing as measured by (1) wound contraction and (2) histopathological findings. METHODS: Full-thickness wounds measuring 1.5 cm square were created on the dorsum of Yorkshire pigs and were enclosed in polyurethane wound chambers. Amitriptyline was applied daily at various concentrations. Bupivacaine (0.5%) or normal saline were used as controls. Daily wound serum levels were obtained and the level of amitriptyline and nortriptyline obtained. Pictures were taken daily and the wound surface analyzed for contraction. Cross-sectional, full-thickness skin biopsies were obtained at days 2, 8 and 10 and evaluated microscopically for re-epithelialization, inflammation, and necrosis. RESULTS: The high serum level of amitriptyline and nortriptyline did not affect wound healing; re-epithelialization, wound contraction, and inflammation were not significantly different between amitriptyline and control groups. CONCLUSION: Amitriptyline at the concentrations of 0.0625% and 0.125% applied daily via chambers covering wounds in a full-thickness pig excision model has no overt toxic effect on wound healing as measured by wound contraction and histological assessment.

Neurotoxicity of lidocaine involves specific activation of the p38 mitogen-activated protein kinase, but not extracellular signal-regulated or c-jun N-terminal kinases, and is mediated by arachidonic acid metabolites.

BACKGROUND: Pharmacologic inhibition of the p38 mitogen-activated protein kinase (MAPK) leads to a reduction in lidocaine neurotoxicity in vitro and in vivo. The current study investigated in vitro the hypotheses that lidocaine neurotoxicity is specific for dorsal root ganglion cells of different size or phenotype, involves time-dependent and specific activation of the p38 MAPK, that p38 MAPK inhibitors are only effective if applied with local anesthetic, and that p38 MAPK activation triggers activation of lipoxygenase pathways. METHODS: The authors used primary sensory neuron cultures and pheochromocytoma cell line cultures to detect time-dependent activation of the p38 MAPK or related pathways such as extracellular signal-regulated kinases and c-jun N-terminal kinases. Cells were divided by size or by immunoreactivity for calcitonin gene-related peptide or isolectin B4, indicative of nociceptive phenotype. The authors also investigated whether arachidonic acid pathways represent a downstream effector of the p38 MAPK in local anesthetic-induced neurotoxicity. RESULTS: All types of dorsal root ganglion cells were subject to neurotoxic effects of lidocaine, which were mediated by specific activation of the p38 MAPK but not extracellular signal-regulated kinases or c-jun N-terminal kinases. Neuroprotective efficacy of p38 MAPK inhibitors declined significantly when administered more than 1 h after lidocaine exposure. Activation of p38 MAPK preceded activation of arachidonic acid pathways. Neurotoxicity of lidocaine, specific activation of p38 MAPK, and neuroprotective effects of a p38 MAPK inhibitor were further confirmed in pheochromocytoma cell line cultures. CONCLUSIONS: Specific and time-dependent activation of the p38 MAPK is involved in lidocaine-induced neurotoxicity, most likely followed by activation of lipoxygenase pathways.

ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model.

Activation of extracellular signal-regulated kinase (ERK), a mitogen activated-protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by transcription-dependent and -independent means. We have now investigated if ERK is activated in the spinal cord after a spinal nerve ligation (SNL) and if this contributes to the neuropathic pain-like behavior generated in this model. An L5 SNL induces an immediate (<10 min) but transient (<6 h) induction of phosphoERK (pERK) restricted to neurons in the superficial dorsal horn. This is followed by a widespread induction of pERK in spinal microglia that peaks between 1 and 3 days post-surgery. On Day 10, pERK is expressed both in astrocytes and microglia, but by Day 21 predominantly in astrocytes in the dorsal horn. In the L5 DRG SNL transiently induces pERK in neurons at 10 min, and in satellite cells on Day 10 and 21. Intrathecal injection of the MEK (ERK kinase) inhibitor PD98059 on Day 2, 10 or 21 reduces SNL-induced mechanical allodynia. Our results suggest that ERK activation in the dorsal horn, as well as in the DRG, mediates pain through different mechanisms operating in different cells at different times. The sequential activation of ERK in dorsal horn microglia and then in astrocytes might reflect distinct roles for these two subtypes of glia in the temporal evolution of neuropathic pain.

Topical amitriptyline in healthy volunteers.

BACKGROUND AND OBJECTIVES: The antidepressant amitriptyline is used as an adjuvant in the treatment of a variety of chronic pain conditions. This drug interacts with many receptors and ion channels, such as Na+ channels. In a randomized, double-blinded, and placebo-controlled trial, we investigated whether amitriptyline also is capable of providing cutaneous analgesia when applied topically in 14 healthy volunteers. METHODS: Amitriptyline hydrochloride was prepared as a 45% water/45% isopropanol/10% glycerin solution and titrated to pH 8.5 with sodium hydroxide. Four areas, 2 on each arm, of approximately 1 cm(2) each were marked on the ventral aspect of the upper arm. A piece of gauze, placed on each of the marked areas and affixed to the arm with an occlusive plastic dressing, was saturated via syringe with placebo and amitriptyline solutions (10 mmol/L, 50 mmol/L, and 100 mmol/L). After 1 hour, the dressings and gauze were removed. A 16-G blunt needle was used to grade the pain at the marked area once per hour (1 = complete analgesia, 10 = normal pain sensation). RESULTS: The analgesic effects of 50 mmol/L and 100 mmol/L solutions of amitriptyline were significantly higher than those of the placebo or the 10 mmol/L solution. However, no significant difference was found between the analgesia provided by the placebo solution versus the 10 mmol/L solution or between the 50 mmol/L versus the 100 mmol/L solution. The only side effect observed was a concentration-dependent redness of the skin. CONCLUSIONS: Topically applied amitriptyline is effective as an analgesic in humans. Different vehicles may improve its efficacy and decrease the skin redness observed.