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Anesth Analg ; 132(4): 1138-1145, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617181


BACKGROUND: Epidural block are often used for analgesia after open nephrectomy surgery. Subcostal anterior quadratus lumborum block may be an alternative. We therefore tested the hypothesis that the continuous subcostal anterior quadratus lumborum block is noninferior to epidural block for analgesia in patients having open partial nephrectomies. METHODS: Adults having open partial nephrectomies were randomly allocated to epidural or unilateral subcostal anterior quadratus lumborum block. The joint primary outcomes were opioid consumption measured in morphine equivalents and pain measured on a numeric rating scale (0-10) from postanesthesia care unit (PACU) until 72 hours after surgery. The noninferiority deltas were 30% for opioid consumption and 1 point on a 0-10 scale for pain. Secondary outcomes included patient global assessment of pain management on the third postoperative day, the number of antiemetic medication doses through the third postoperative day, duration of PACU stay, and postoperative duration of hospitalization. RESULTS: Twenty-six patients were randomized to anterior quadratus lumborum block and 29 to epidural analgesia. Neither pain scores nor opioid consumption in the quadratus lumborum patients were noninferior to epidural analgesia. At 72 hours, mean ± standard deviation pain scores in subcoastal anterior quadratus lumborum block and epidural group were 4.7 ± 1.8 and 4.1 ± 1.7, with an estimated difference in pain scores of 0.62 (95% confidence interval [CI], 0.74-1.99; noninferiority P = .21). The median [Q1, Q3] opioid consumption was more than doubled in quadratus lumborum patients at 70 mg [43, 125] versus 30 mg [18, 75] in the epidural group with an estimated ratio of geometric means of 1.69 (95% CI, 0.66-4.33; noninferiority P = .80). Patient global assessment and duration of PACU and hospital stays did not differ significantly in the 2 groups. CONCLUSIONS: We were unable to show that subcostal anterior quadratus lumborum block are noninferior to epidural analgesia in terms of pain scores and opioid consumption for open partial nephrectomies. Effectiveness of novel blocks should be rigorously tested in specific surgical setting before widespread adoption.

Analgesia Epidural , Nefrectomia , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Idoso , Analgesia Epidural/efeitos adversos , Analgésicos Opioides/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/efeitos adversos , Bloqueio Nervoso/efeitos adversos , Ohio , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
J Anesth ; 33(1): 148-154, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30659364


In the case of open urological surgeries, analgesic coverage at mid thoracic dermatomal levels is required. As shown in cadaveric studies, the site of QL block injection is an important determinant of the extent of dye spread and presumably local anesthetic dermatomal coverage. In this case series, we evaluated dermatomal blockade and analgesic efficacy of a subcostal approach to anterior QL block following open urological surgeries. Twenty-two adult patients undergoing renal transplant surgery (60%) and open nephrectomy (40%) received unilateral ultrasound-guided subcostal anterior QL block with catheter insertion. Sensory level, pain score (numeric rating scale, NRS), local anesthetic consumption, and opioid consumption (morphine equivalent dose, MED) were assessed daily for 3 days. The block achieved sensory blockade between T6-7 and L1-2. The most frequently affected dermatomes were T8 -T12 and the number of blocked segments was 3 (mean 2.8). The median (interquartile range Q1, Q3) of NRS pain score was 3.7 (2.8-5.5), 3.3 (2.4-4.7), 2.9 (1.9-3.6), and 2.3 (1.0-4.2) on POD0, POD1, POD2, and POD3, respectively. Our preliminary data showed that the subcostal approach to anterior QL block provides appropriate thoracic dermatome level needed for analgesia following open urological surgical procedures between T6-7 and L1-2.

Anestésicos Locais/administração & dosagem , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Adulto , Idoso , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-Idade
Ultrasound Med Biol ; 44(7): 1411-1422, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29681422


Spectral analysis of ultrasound radiofrequency backscatter has the potential to identify intercostal blood vessels during ultrasound-guided placement of paravertebral nerve blocks and intercostal nerve blocks. Autoregressive models were used for spectral estimation, and bandwidth, autoregressive order and region-of-interest size were evaluated. Eight spectral parameters were calculated and used to create random forests. An autoregressive order of 10, bandwidth of 6 dB and region-of-interest size of 1.0 mm resulted in the minimum out-of-bag error. An additional random forest, using these chosen values, was created from 70% of the data and evaluated independently from the remaining 30% of data. The random forest achieved a predictive accuracy of 92% and Youden's index of 0.85. These results suggest that spectral analysis of ultrasound radiofrequency backscatter has the potential to identify intercostal blood vessels. ( © 2018 World Federation for Ultrasound in Medicine and Biology.

Vasos Sanguíneos/diagnóstico por imagem , Nervos Intercostais/irrigação sanguínea , Nervos Intercostais/diagnóstico por imagem , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Adulto , Humanos , Projetos Piloto , Valores de Referência
Eur J Anaesthesiol ; 34(9): 587-595, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28731927


BACKGROUND: The dermatomal level of analgesia achieved with quadratus lumborum blocks varies according to the location of injection. The most commonly used approaches are either at the postero-lateral aspect or anterior to the quadratus lumborum muscle. OBJECTIVE: To determine whether the site of injection of contrast dye around the quadratus lumborum muscle of cadavers affects the extent and mechanism of dye spread. DESIGN: Observational human cadaver study. SETTING: Cleveland Clinic cadaveric laboratory. PARTICIPANTS: Six fresh human cadavers. INTERVENTIONS: The cadavers received either a posterior quadratus lumborum block or an anterior subcostal quadratus lumborum block on each side. MAIN OUTCOME MEASURES: Cadavers were dissected to determine the extent of dye spread. RESULTS: The posterior quadratus lumborum block approach revealed consistently deep staining of the iliohypogastric, ilioinguinal, subcostal nerve, T11 to 12 and L1 nerve roots. In addition, staining of the middle thoracolumbar fascia was seen in all specimens but only variable staining of T10 nerve roots. The anterior subcostal quadratus lumborum block approach in all specimens demonstrated predictable deep staining of the iliohypogastric and ilioinguinal nerves, subcostal nerves, T11 to 12 and L1 nerve roots, and in addition traversing the arcuate ligaments to involve T9 to 12 nerve roots with variable staining of higher thoracic nerve roots. CONCLUSIONS: Our cadaveric study demonstrates that injection of dye on the posterior aspect of quadratus lumborum muscle led to injectate spread through the lateral and posterior abdominal wall but with limited cranial spread, whereas the anterior approach produced broader coverage of the lower to mid-thoracic region. Clinical translation of these findings to determine the practical significance is warranted.

Injeções Intramusculares/métodos , Bloqueio Nervoso/métodos , Músculos Abdominais/diagnóstico por imagem , Músculos Abdominais/inervação , Adulto , Cadáver , Corantes/administração & dosagem , Dissecação , Feminino , Humanos , Plexo Lombossacral/diagnóstico por imagem , Masculino , Ultrassonografia de Intervenção
J Biol Chem ; 288(2): 1032-46, 2013 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-23204520


Kinase/phosphatase balance governs cardiac excitability in health and disease. Although detailed mechanisms for cardiac kinase regulation are established, far less is known regarding cardiac protein phosphatase 2A (PP2A) regulation. This is largely due to the complexity of the PP2A holoenzyme structure (combinatorial assembly of three subunit enzyme from >17 subunit genes) and the inability to segregate "global" PP2A function from the activities of multiple "local" holoenzyme populations. Here we report that PP2A catalytic, regulatory, and scaffolding subunits are tightly regulated at transcriptional, translational, and post-translational levels to tune myocyte function at base line and in disease. We show that past global read-outs of cellular PP2A activity more appropriately represent the collective activity of numerous individual PP2A holoenzymes, each displaying a specific subcellular localization (dictated by select PP2A regulatory subunits) as well as local specific post-translational catalytic subunit methylation and phosphorylation events that regulate local and rapid holoenzyme assembly/disassembly (via leucine carboxymethyltransferase 1/phosphatase methylesterase 1 (LCMT-1/PME-1). We report that PP2A subunits are selectively regulated between human and animal models, across cardiac chambers, and even within specific cardiac cell types. Moreover, this regulation can be rapidly tuned in response to cellular activation. Finally, we report that global PP2A is altered in human and experimental models of heart disease, yet each pathology displays its own distinct molecular signature though specific PP2A subunit modulatory events. These new data provide an initial view into the signaling pathways that govern PP2A function in heart but also establish the first step in defining specific PP2A regulatory targets in health and disease.

Miocárdio/enzimologia , Proteína Fosfatase 2/metabolismo , Animais , Sequência de Bases , Primers do DNA , Cães , Humanos , Imunoprecipitação , Camundongos , Reação em Cadeia da Polimerase , Biossíntese de Proteínas , Proteína Fosfatase 2/genética , Transdução de Sinais , Transcrição Genética
Heart Rhythm ; 9(12): 2034-41, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23059182


BACKGROUND: Cardiovascular disease is a leading cause of death worldwide. Arrhythmias are associated with significant morbidity and mortality related to cardiovascular disease. Recent work illustrates that many cardiac arrhythmias are initiated by a pathologic imbalance between kinase and phosphatase activities in excitable cardiomyocytes. OBJECTIVE: To test the relationship between myocyte kinase/phosphatase imbalance and cellular and whole animal arrhythmia phenotypes associated with ankyrin-B cardiac syndrome. METHODS: By using a combination of biochemical, electrophysiological, and in vivo approaches, we tested the ability of calcium/calmodulin-dependent kinase (CaMKII) inhibition to rescue imbalance in kinase/phosphatase pathways associated with human ankyrin-B-associated cardiac arrhythmia. RESULTS: The cardiac ryanodine receptor (RyR(2)), a validated target of kinase/phosphatase regulation in myocytes, displays abnormal CaMKII-dependent phosphorylation (pS2814 hyperphosphorylation) in ankyrin-B(+/-) heart. Notably, RyR(2) dysregulation is rescued in myocytes from ankyrin-B(+/-) mice overexpressing a potent CaMKII-inhibitory peptide (AC3I), and aberrant RyR(2) open probability observed in ankyrin-B(+/-) hearts is normalized by treatment with the CaMKII inhibitor KN-93. CaMKII inhibition is sufficient to rescue abnormalities in ankyrin-B(+/-) myocyte electrical dysfunction including cellular afterdepolarizations, and significantly blunts whole animal cardiac arrhythmias and sudden death in response to elevated sympathetic tone. CONCLUSIONS: These findings illustrate the complexity of the molecular components involved in human arrhythmia and define regulatory elements of the ankyrin-B pathway in pathophysiology. Furthermore, the findings illustrate the potential impact of CaMKII inhibition in the treatment of a congenital form of human cardiac arrhythmia.

Anquirinas/genética , Arritmias Cardíacas/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Miócitos Cardíacos/metabolismo , Fibrilação Ventricular/genética , Animais , Anquirinas/deficiência , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Humanos , Immunoblotting , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/patologia , Técnicas de Patch-Clamp , Fenótipo , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/fisiopatologia