In patients with diabetes, metabolic disorders disturb the physiological balance of coagulation and fibrinolysis, leading to a prothrombotic state characterized by platelet hypersensitivity, coagulation disorders and hypofibrinolysis. Hyperglycemia and insulin resistance cause changes in platelet number and activation, as well as qualitative and/or quantitative modifications of coagulatory and fibrinolytic factors, resulting in the formation of fibrinolysis-resistant clots in patients with diabetes. Other coexisting factors like hypoglycemia, obesity and dyslipidemia also contribute to coagulation disorders in patients with diabetes. Management of the prothrombotic state includes antiplatelet and anticoagulation therapies for diabetes patients with either a history of cardiovascular disease or prone to a higher risk of thrombus generation, but current guidelines lack recommendations on the optimal antithrombotic treatment for these patients. Metabolic optimizations like glucose control, lipid-lowering, and weight loss also improve coagulation disorders of diabetes patients. Intriguing, glucose-lowering drugs, especially cardiovascular beneficial agents, such as glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter inhibitors, have been shown to exert direct anticoagulation effects in patients with diabetes. This review focuses on the most recent progress in the development and management of diabetes related prothrombotic state.

Ing and postconditioning alone and whether there is a synergistic effect of both. Rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Infarct size was determined by triphenyltetrazolium staining. The following protocols were used: 1) preconditioning (S-Pre, n = 10, achieved by 2 periods of 5 min sevoflurane administration (1 MAC) followed by 10 min of washout); 2) sevoflurane postconditioning (1 MAC of sevoflurane given for 2 min at the beginning of reperfusion; S-Post, n = 10); 3) administration before and after ischemia (S-Pre + S-Post, n = 10). Protocols 1–3 were repeated in the presence of 5-hydroxydecanoate (5HD), a specific mKATP-channel-blocker (S-Pre + S-Post + 5HD, S-Pre + 5HD: n = 10; S-Post + 5HD: n = 9). Nine rats served as untreated controls (CON) or received 5HD alone (5HD, n = 10). Both S-Pre (23% ± 13% of the area at risk, mean ± sd) and S-Post (18% ± 5%) reduced infarct size compared with CON (49% ± 11%, both P < 0.05). S-Pre + S-Post resulted in a larger reduction of infarct size (12% ± 5%, P = 0.054 versus S-Pre) compared with administration before or after ischemia alone. 5HD diminished the protection in all three sevoflurane treated groups (S-Pre + 5HD, 35% ± 12%; S-Post + 5HD, 44% ± 12%; S-Pre + S-Post + 5HD, 46% ± 14%;) but given alone had no effect on infarct size (41% ± 13%). Sevoflurane preconditioning and postconditioning protects against myocardial ischemia-reperfusion injury. The combination of preconditioning and postconditioning provides additive cardioprotection and is mediated, at least in part, by mKATP-channels....

Background: Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals. Methods: Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7). Results: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001). Conclusion: Isoflurane-induced preconditioning depends on the release of free radicals.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most complex gastrointestinal endoscopic procedures. Currently, it is still unclear which sedation regimen best facilitates an ERCP. TheN-methyl-d-aspartate receptor antagonist esketamine has anaesthetic, analgesic and sympathomimetic properties and is known to cause less cardiorespiratory depression than other sedatives. It could therefore be an ideal adjunct to propofol for deep sedation.OBJECTIVE: To assess the effectiveness of esketamine versus alfentanil as an adjunct to propofol target-controlled infusion (TCI) for deep sedation during ambulant ERCP.DESIGN: A randomised controlled multicentre study.SETTING: Endoscopic intervention suite at an academic and general hospital in the Netherlands.PARTICIPANTS: Adult, American Society of Anesthesiologists Physical Status I to III patients scheduled to undergo ERCP.INTERVENTION: Consecutive patients were randomly assigned to receive sedation for an ERCP with propofol TCI and alfentanil (group A) or with propofol TCI and esketamine (group E).MAIN OUTCOME MEASURES: The primary outcome was effectiveness of the sedation regimen expressed as the total dose of propofol – as a surrogate parameter – necessary to perform ERCP in a satisfactory manner for endoscopist and patients. Secondary outcomes were recovery time, patients’ and endoscopists’ satisfaction with sedation, side effects (e.g. psychotomimetic effects, nausea and vomiting) and the number of respiratory and cardiovascular adverse events.RESULTS: Data from 162 patients were analysed. The total dose of propofol required was significantly lower in group E (n=83) (8.3 mg kg⁻¹ h⁻¹) than in group A (n=79) (10.5 mg kg⁻¹ h⁻¹) (P < 0.001). There were no significant differences in recovery time, patients’ and endoscopists’ satisfaction, side effects, psychotomimetic effects and the number of sedation-related adverse events.CONCLUSION: Low-dose esketamine reduces the total amount of propofol necessary for sedation during ERCP in American Society of Anesthesiologists I and II patients without affecting recovery time, satisfaction of patients and endoscopists, side effects and respiratory or cardiovascular adverse events, when compared with alfentanil.TRIAL REGISTRATION: The Netherlands Trial Register (NTR5486).