Kinetics of Local Anesthetic Interactions with Model Membranes: Adsorption and Permeation
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Abstract
Introduction: Local anesthetics (LAs) must be adsorbed to and permeate through membranes to reach their sites of action. The rates of these processes critically affect drug actions at the cellular level and also the in vivo pharma cokinetics of perineurally injected drugs. Therefore, we measured the adsorption equilibria and permeation kinetics of two LAs local anesthetics with markedly different hydrophobicities: tetracaine (TTC, Poctanol:buffer = 3.6 × 103) and procaine (PRO, Poctanol:buffer = 8.1 × 101), in unilamellar membranes of different composition and fluidity. Methods: Interactions with unilamellar ve sicles made of dipalmitoylphosphatidylcholine (DPPC), at 23˚C (solid gel state) or 45˚C (liquid crystal state), without or with cholesterol (Chol), were investigated by a combination of fluorescence and stopped-flow techniques. Membrane adsorption was monitored by the LA’s fluorescence. Membrane permeation was monitored by the decrease of fluorescence intensity of intra vesicular pyranine, when quenched by neighboring TTC or PRO. Results:Ionized TTC (TTCH+) and procaine (PROH+) adsorb to membranes more slowly and weakly than their neutral counterparts (time constant τ ~ 0.1 sec). Fluidizing of membranes, at the higher temperature (45˚C) or by Chol inclusion, accelerated LA adsorption (faster than the mixing time of the stopped flow device, 0.008 s). Permeation of protonated TTCH+ through the solid gel DPPC membranes (23˚C) occurred far more slowly than adsorption, (τ = 36.7 ± 0.7 s, n = 9), and 3 times slower than neutral TTC (τ = 10.9 ± 0.7 s, n = 9); neutral PRO permeated these membranes at the same rate as TTC. Inclusion of Chol with DPPC, disordering the fatty acyl tails of membrane phos pholipids while crowding their polar headgroups, slowed permeation of TTC and of PRO to an even greater degree. Conclusions: Local anesthetic permeation through membranes is limited by the transport across the membrane core and not by the initial binding. Drug ionization greatly slows permeation, but greater hydrophobicity does not facilitate it. Lipid crowding caused by Chol, a normal membrane component, slows permeation by disorienting the LA bound at the surface.
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Gary Strichartz,
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General Anesthesia for Cesarean Section in a Pregnant Woman with Immune Thrombocytopenic Purpura (ITP): A Case Report and Review of the Literature
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Background: Management of immune thrombocytopenia (ITP) during pregnancy can be challenging, particularly by identifying a threshold for safe administration of neuraxial/general anesthesia and minimizing postpartum hemorrhage. There is controversy over the safety of cesarean section (CS) in ITP patients. In this case report, we discuss general anesthesia management in a patient with ITP with severe thrombocytopenia. Case Presentation: A 28-year-old female with relapsed/refractory ITP and severe thrombocytopenia underwent general anesthesia and emergent cesarean section with successful outcomes and minimal bleeding. Platelet counts before CS were 5000 × 109 L, the patient received 1 unit of platelets before the procedure and 1 unit of platelet and tranexamic acid 500 mg was injected slowly during the procedure. No evidence of bleeding and no complications were observed in the patient or newborn. Conclusions: In an emergent circumstance, general anesthesia and cesarean section procedure were performed safely in a patient with severe thrombocytopenia, no hemorrhagic complications were seen for this patient or neonate. Objective of This Manuscript: To share our experience of a safe emergent CS procedure and general anesthesia in a patient with severe thrombocytopenia. Our experience may guide the management of ITP patients in emergent delivery circumstances.
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Jose M. Torres Zazueta,
Jena Konkler,
Jesus Vera Aguilera,
Carlos Vera Aguilera,
Sergio Ariel Soto Hopkins,
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The Impact of Fresh Gas Flow Sevoflurane Anesthesia on Perioperative Hypothermia in Adult Patients Undergoing Elective Open or Laparoscopic Digestive Surgery: A Prospective Randomized Controlled Trial
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Background: Because body temperature is such an important indicator and a basic requirement for all kinds of life, even tiny variances might induce undesired changes. This study looked at the influence of FGFs sevoflurane anesthesia on heat preservation in patients undergoing open or laparoscopic digestive surgery. Materials and Methods: Two hundred and forty adult patients (18 - 75 years) with an ASA of I-II were scheduled for open and laparoscopic digestive surgery: open surgery (Group O, n = 120 patients) and laparoscopic surgery (Group L, n = 120 patients). Each group was separated randomly into four subgroups (n = 30 patients) based on FGFs (0.7, 1, 1.5, or 2 L/min). Each patient’s HR, MBP, SpO2, FiO2, fluid infusion amount, urine volume, pre/post-Hb, surgery time, and nasopharyngeal temperatures were investigated and recorded every 15 min from 0 to 120 min. Results: Between groupings, there were no significant changes in demographic fea tures. In 240 patients, the results of various FGFs (0.7, 1, 1.5, and 2 L/min), no statistically significant differences were found in core body temperature over time within each subgroup, with no statistically significant differences between the two (open and laparoscopic) (P > 0.05). Conclusions: The study concluded that FGFs (0.7, 1, 1.5, and 2 L/min) could be utilized safely in adult patients undergoing open or laparoscopic digestive surgery. FGFs (0.7, 1, 1.5, and 2 L/min) provide better body heat preservation during surgical operations.
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Feng Qi,
Ahmed Badughaish,
Qiya Hu,
Lianying Zhao,
Yuanyuan Meng,
Yu Liu,
Shuqin Wang,
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Persistent Post-Surgical Pain after Total Knee Arthroplasty at a Tertiary Care Hospital of a Low-Middle Income Country
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Background: Persistent post-surgical pain (PPSP) is pain that lasts for 3 months or more after a surgical intervention, where other causes of pain have been excluded. There is scarce knowledge about the prevalence of PPSP in low- and middle-income countries (LMICs). The aim of our study was to assess the prevalence of PPSP after total knee arthroplasty (TKA) at our university hospital and explore factors associated with it. Methods: It was a prospective cross-sectional study. Approval was obtained from the Ethics Review Committee. Patients undergoing elective unilateral total knee arthroplasty under general or regional anaesthesia were recruited over a six months period. A designated pain nurse called the patients three months after surgery and asked about the presence of pain, its location, type, degree and associated factors. Patients who reported pain at three months were called a year after the surgery and the same questions were asked. Results: Eighty-two patients had TKA during the study period. At the time of discharge, 57 (69.5%) patients were satisfied with their postoperative pain management. Three months after the surgery, 13 (15.8%) patients reported pain. Pain was mild in 11 and moderate in two patients. At one-year follow-up, three patients (3.6%) reported pain that was mild to moderate in intensity. Pain disturbed sleep in all three patients and disturbed daily life routines in one patient. No significant difference was found in any of the variables when compared with patients who did not report pain at three months. Conclusions: Although PPSP is a recognized adverse outcome after TKA, little is known about its prevalence in LMICs. In our patient population, 15.8% reported pain three months after TKA, while at one year, 3.6% of patients reported mild to moderate pain. Multicenter studies are recommended for determining the overall prevalence in our patient population and for getting directions for making targeted efforts towards its prevention and treatment.
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Aliya Ahmed,
Gauhar Afshan,
Robyna Khan,
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Ultrasound, Fluoroscopic-Guided Caudal, Lumbar Epidural Steroid Injections and Blinding Paraspinal Lumbosacral Steroid Injections in Patients with Low Back Pain with Radiculopathy
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Background and Aims: Low back pain (LBP) is considered one of the most common health conditions in the world right now, and it affects many individuals throughout different stages of their lives. Chronic LBP (CLBP) was estimated to be between 5% and 10%, defined as LBP that lasts for 12 weeks. The most common causes of CLBP with radiculopathy are lumbar disc pro lapse (LDP) and degenerative facet osteoarthropathy (DFO); the aim of this study is to investigate the efficacy of ultrasound (US) guided, fluoroscopy (FL) guided, Caudal Epidural Steroid Injection (CESI), lumbar epidural steroid injections (LESI), and blinding lumbosacral steroid injections (LSPSI) in patients with CLBP with radiculopathy. Patients and Methods: This is a randomized prospective study that was conducted at the department of rheumatology at Al Azhar University Hospital in Egypt between November 2020 and August 2021. A total of 100 patients with refractory CLBP with radiculopathy were enrolled in the study. Consequently, they were divided into 2 groups: the first consisted of fifty patients with CLBP and radiculopathy caused by LDP, as determined by lumbosacral magnetic resonance imaging (MRI), and the second group consisted of fifty patients with refractory low back pain and radiculopathy caused by DFO, as determined by lumbosacral plain x-rays and lumbosacral MRI. The following procedures were per formed: US-guided CESI, FL-guided CESI, FL-guided LESI, US-guided LESI, and blinding LSPSI. Results: In the LDP group, there is a statistically significant difference between considered spinal nerve roots as regards Visual Analogue Scale (VAS) (at 2 months). Likewise, a statistically significant difference was found between blinding LSPSI and US-Guided LESI with respect to VAS (baseline) and VAS (2 months) (P-value = 0.018 and 0.003, respectively). Statistically significant differences were reported in VAS (2 months) for both FL-guided LESI and FL-guided CESI groups. Considering the VAS of studied spinal nerve roots in the DFO group, there is a statistically significant difference between the examined spinal nerve roots with respect to Oswestry Disability Index (ODI) (2 months). Similarly, there is a statistically significant difference in VAS (2 months) between US-guided LESI and para-spinal roots and FL-guided LESI and para-spinal roots (P-value = 0.038 and 0.021, respectively). Additionally, there is a statistically significant difference between the US-guided CESI, FL-guided CESI, FL-guided LESI, and spinal nerve roots with respect to ODI (at 2 months). (P-value = 0.033, 0.025 and 0.005, respectively). Conclusion: US is excellent in guiding CESI and LESI and should be the preferred alternative when FL is not provided, with a similar treatment outcome compared to FL-CESI and LESI.
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Bilateral Sphenopalatine Ganglion Block for the Treatment of Post Dural Puncture Headache: A Case Report
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Background: Post dural puncture headache (PDPH) is a known and potentially debilitating complication of neuraxial anesthesia that can impede patient recovery. The conventional treatment includes hydration and symptomatic treatment like simple analgesics. Those who have unremitting symptoms following conservative measures are offered an epidural blood patch (EBP). However, EBP, an invasive procedure, is associated with complications in itself. Case: We report a 40-year-old man who experienced PDPH after spinal anesthesia. His symptoms recurred after conservative management was instituted. He was then offered a trans-nasal sphenopalatine ganglion (SPG) block. He had excellent pain relief and did not require an EBP. Conclusion: SPG blocks can be considered early in the treatment of PDPH together with general supportive measures. However, if pain relief is not achieved, an epidural blood patch should still be considered.
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Shivani Manohara,
Yean Chin Lim,
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