Atropine 500micrograms/0.3ml / Adrenaline (base) 60micrograms/0.3ml / Procaine hydrochloride 3mg/0.3ml solution for injection ampoules

BACKGROUND: Spinal anesthesia, as an effective approach, is widely performed in various surgeries with possible complications. To reduce the side effects, many adjuvants are used to maintain desirable sensory and motor blockades and increase the quality and prolong the analgesia. METHODS: In the current double-blind, randomized clinical trial, 105 participants aged 18 - 60 years with ASA class I or II who were candidate for lower limb surgery were randomly allocated to patients receiving bupivacaine 15 mg + normal saline 1 mL (B group), bupivacaine 15 mg + epinephrine 10 µg (BE group), and bupivacaine 15 mg + sufentanyl 5 µg (BS group). Onset of sensory blockade was determined bilaterally with the pinprick test. The maximum Bromage scale was assessed for the onset of motor blockage. Recovery from sensory and motor blockades was also evaluated. Pain score (visual analogue scale; VAS) was determined for all participants. RESULTS: Onset of sensory and motor blockades was statistically different among the groups. Intrathecal bupivacaine (the placebo group) had the lowest onset of sensory blockage, whereas the onset of motor blockade was significantly shorter with the administration of sufentanil + epinephrine (P = 0.001) (BS and BE groups). However, epinephrine (BE group) did not significantly prolong sensory and motor blockade. Recovery time from sensory and motor blockade was significantly lower with the bupivacaine alone (the placebo group). CONCLUSIONS: The current study results suggested that the combination of 10 µg epinephrine and 5 µg sufentanil + bupivacaine did not prolong the sensory and motor blockades in spinal anesthesia for lower limb surgery, compared with bupivacaine alone.

Abstract licence: CC BY-NC

The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists - originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists - searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g. dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists - investigations of their pharmacology as “sedatives” (e.g. chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g. domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3 (5-HT3) receptor antagonists - metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (contributing to anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g. granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1 receptor antagonists - antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years.

Abstract licence: CC BY

Adrenaline (Ad) strengthens contextual fear memory by increasing blood glucose, possibly enhancing hippocampus acetylcholine synthesis. Nevertheless, it is unclear if peripheral Ad influences the cholinergic system, contributing to contextual fear memory strengthening. We aimed to evaluate whether peripheral Ad alters muscarinic receptor expression and if the cholinergic system is involved in peripheral Ad contextual fear memory strengthening effect. Wild-type (WT) and Ad-deficient male mice (129 × 1/SvJ) underwent a fear conditioning procedure followed by intraperitoneal pre-training and pre-context administration of Ad (0.1 mg/kg), atropine (10 mg/kg), methylatropine (0.5 mg/kg), Ad (0.1 mg/kg) plus atropine (10 mg/kg) or vehicle (NaCl, 0.9%). Shock responsiveness and freezing behaviour were accessed. Hippocampal M 1 , M 2 , and M 4 mRNA expression were evaluated. Ad-deficient mice presented decreased hippocampal muscarinic M 4 subtype receptor mRNA expression compared to WT mice. In Ad-administered Ad-deficient mice, hippocampal muscarinic M 4 subtype receptor mRNA expression increased compared with vehicle-administered Ad-deficient mice. On the context day, atropine-administered WT mice presented decreased freezing behaviour compared to vehicle or methylatropine-administered WT mice. Moreover, Ad plus atropine-administered Ad-deficient mice led to decreased freezing behaviour compared to Ad-administered Ad-deficient mice. In conclusion, Ad-deficient mice's contextual fear memory impairment was associated with hippocampal muscarinic M 4 subtype receptor down expression, which was reversed by Ad. This may be related to contextual fear memory consolidation or retrieval induced by peripheral Ad. Furthermore, the effect of Ad contextual fear memory might be due to increased hippocampus muscarinic subtype M 4 expression, which may contribute to increased cholinergic activity in the central nervous system. • Adrenaline-deficient mice showed impaired contextual fear memory and M 4 expression. • Contextual fear memory and hippocampal M 4 expression was restored by adrenaline. • Central muscarinic antagonist reverts fear memory enhancement induced by adrenaline. • Adrenaline fear memory strengthening effect might be due to increased M 4 expression. • M 4 expression contributes to high cholinergic activity in the central nervous system.

Abstract licence: CC BY

Protamine is widely used after catheter ablation to achieve hemostasis. Anaphylaxis to protamine is a rare but severe complication. A 49-year-old male patient underwent catheter ablation of symptomatic long-standing persistent atrial fibrillation. Sinus bradycardia emerged 20 minutes after the protamine infusion and was unresponsive to atropine. Subsequently, pulseless electrical activity and severe global hypokinesis developed and were refractory to pacing and repeated infusions of intravenous adrenaline. Extracorporeal membrane oxygenation and a catecholamine infusion were required for the following 2 days. An intradermal test with protamine showed positive results, and adrenaline-refractory anaphylaxis (ARA) was diagnosed. The incidence of protamine anaphylaxis is 0.14%, and ARA may occur, especially in patients receiving beta-blockers. Although there is no established approach, glucagon, methylene blue, and the rapid introduction of extracorporeal membrane oxygenation should be considered when ARA is suspected.

Abstract licence: CC BY-NC-ND

BACKGROUND: Profound bradycardia caused by sugammadex has been reported, although its mechanism is unclear. Herein, we suggest a possible culprit for this phenomenon. CASE PRESENTATION: A 50-year-old woman without comorbidity except mild obesity underwent a transabdominal hysterectomy and right salpingo-oophorectomy. After surgery, sugammadex 200 mg was intravenously administered. Approximately 4 min later, her heart rate decreased to 36 bpm accompanied by hypotension (41/20 mmHg) and ST depression in limb lead electrocardiogram (ECG). Atropine 0.5 mg was injected intravenously without improving the hemodynamics. Intravenous adrenaline 0.5 mg was added despite the lack of signs suggesting allergic reactions. Her heart rate and blood pressure quickly recovered and remained stable thereafter, although 12-lead ECG taken 1 h later still showed ST depression. CONCLUSIONS: In this case, the significant bradycardia appeared attributable to coronary vasospasm (Kounis syndrome) induced by sugammadex, considering the ECG findings and high incidence of anaphylaxis due to sugammadex.

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BACKGROUND: Intraoperative Floppy Iris Syndrome (IFIS) is an important cause of surgical complications and iris defects in patients undergoing phacoemulsification that were treated with selective subtype α1A receptor antagonists for a long period of time. To date, no definitive preventive strategy has emerged, yet. The need of prophylaxis is dictated by the high prevalence of males affected by benign prostatic hyperplasia undergoing cataract surgery. OBJECTIVE: To identify the best prophylactic strategy in groups at risk of IFIS development by comparing two mydriatic treatments in course of phacoemulsification surgery. METHODS: 81 eyes of 81 patients in treatment with Tamsulosin were enrolled in the study. 43 eyes were treated with atropine sulfate 1% while 38 eyes received an injection of mydriatic solution containing epinephrine in the anterior chamber. All phacoemulsifications were videotaped in order to assess the occurrence of IFIS and the severity of the syndrome. RESULTS: The treatment group showed a statistically significant reduction (p = 0.0115) of floppy iris syndrome incidence, from 86.05% (37/43) of the atropine group to 60.53% (23/38). The analysis showed a reduction of IFIS mild form only, whereas the incidence of severe forms remained unchanged. CONCLUSIONS: We believe that IFIS may arise through two different mechanisms: pharmacological antagonism and anatomical modifications. Patients suffering from mild forms of the disease showed a statistically significant reduction of IFIS incidence after intraoperative prophylaxis due to epinephrine's ability to displace Tamsulosin, resulting in the increase of iris tone when the disease is caused mainly by receptorial antagonism. On the contrary, prophylaxis does not deliver any valuable result in case of severe forms where the anatomical variations play a major role.

Abstract licence: CC BY