Cannabinoid Analgesia in Postoperative Pain Management: From Molecular Mechanisms to Clinical Reality.

Postoperative pain (POP) is a challenging clinical phenomenon that affects the majority of surgical patients and demands effective management to mitigate adverse outcomes such as persistent pain. The primary goal of POP management is to alleviate suffering and facilitate a seamless return to normal function for the patient. Despite compelling evidence of its drawbacks, opioid analgesia remains the basis of POP treatment. Novel therapeutic approaches rely on multimodal analgesia, integrating different pharmacological strategies to optimize efficacy while minimizing adverse effects. The recognition of the imperative role of the endocannabinoid system in pain regulation has prompted the investigation of cannabinoid compounds as a new therapeutic avenue. Cannabinoids may serve as adjuvants, enhancing the analgesic effects of other drugs and potentially replacing or at least reducing the dependence on other long-term analgesics in pain management. This narrative review succinctly summarizes pertinent information on the molecular mechanisms, clinical therapeutic benefits, and considerations associated with the plausible use of various cannabinoid compounds in treating POP. According to the available evidence, cannabinoid compounds modulate specific molecular mechanisms intimately involved in POP. However, only two of the eleven clinical trials that evaluated the efficacy of different cannabinoid interventions showed positive results.

Long-Term Evolution of Patients Treated for Paroxysmal Atrial Fibrillation with First and Second Generation Cryoballoon Catheter Ablation with a Prospective Protocol Guided by Complete Bidirectional Left Atrium-Pulmonary Veins Disconnection after Adenosine as Main Target end Point to achieved. Seven Years Follow-up of Patients with a rough estimation profile of Low ALARMEc Score. A Single Center Report.

INTRODUCTION: Cryoballoon ablation (CB) has proven effective for treating patients with paroxysmal atrial fibrillation (PAF). We analyzed our seven year follow-up of patients, treated for PAF with first (CB1) and second generation (CB2), with demonstration of LA-PV disconnection with bidirectional block (BB) after adenosine (AD). METHODS: Since November 2008 to May 2015, 128 patients, 97 male (58±7 years), without heart disease, highly symptomatic, refractory to antiarrhythmic drugs (AAD) were treated, and follow-up (1411 ±727 days). Left atrial size: 37±6 mm. RESULTS: A total of 439 PV were successfully isolated (91.9%). Acute reconduction: 44 PV (9%): 16 after CB; 16 unmasked by AD; 12 extrapulmonary muscular connections (EMC). Main complication was phrenic nerve palsy (PNP): 9 (7 %). On follow-up, 114 patients (89%) remain asymptomatic in sinus rhythm (SR), free of medication. Fourteen patients (11%) had arrhythmia recurrence: 12 male (52±8 years). Early recurrences occurred in 9 male. Late recurrences presented 3 male at 24, 27 and 60 months, and 2 female at 7 and 40 months respectively. All recurrence patients were Redo, and remain in SR without medication during follow-up. CONCLUSIONS: CB alone is very effective and safe for the definitive treatment of patients suffering PAF with 72.6% success rate, increasing up to 89.1% when this protocol is applied in a single procedure. After Redo, all population group (100%), remain in sinus rhythm, freedom of arrhythmia, without AAD, in this very long term follow-up. Checking for BB, AD protocol, and ruling out EMC allowed-us to identified 14.8% of patients with underlying substrate for potential arrhythmia recurrence. CB2 applications entail a highest risk of PNP. Patients with a rough estimated profile of low ALARMEc score (≤ 1) have an excellent long term outcome, being this series the largest follow-up described so far, for patients treated for PAF with CB.