Influence of ketamine, propofol or isoflurane on intraocular pressure, heart rate and blood pressure in healthy dogs premedicated with medetomidine and midazolam. Veterinary medicine and science BACKGROUND:According to the findings of several studies, sedatives and anaesthetics have different effects on the functioning of the cardiovascular system and intraocular pressure (IOP). For accurate diagnosis, treatment and surgery with minimal complications, it is necessary to be aware of the effects of sedatives and anaesthetics on the cardiovascular system and IOP. OBJECTIVES:The aim of this study was to evaluate the effects of sedatives (medetomidine and midazolam) and anaesthetics (ketamine, propofol and isoflurane) on IOP, heart rate (HR) and blood pressure in dogs. METHODS:In this study, 10 dogs participated in three treatments using a randomised cross-over design, with a 1-week washout period between each treatment. Dogs in all treatments were premedicated with medetomidine and midazolam. Anaesthesia was induced using ketamine, propofol, or isoflurane and maintained for 60 min with the appropriate doses of each drug. The cardiovascular variables (heart rate, and systolic, diastolic and mean arterial pressures) and IOP were measured at different timepoints: before premedication (baseline values, T-Bas), 15 min after medetomidine administration (T-Med), 20 min after midazolam administration (T-Mid) and at 15 (T-15), 30 (T-30), 45 (T-45) and 60 (T-60) min after anaesthesia induction. RESULTS:Medetomidine significantly reduced the IOP and HR and did not significantly change the mean arterial pressure (MAP). Midazolam significantly reduced the IOP while did not significantly change the HR and MAP. Ketamine and isoflurane significantly increased the IOP and HR while did not significantly change the MAP. Propofol significantly increased the HR, but did not cause significant changes in IOP and MAP. CONCLUSIONS:Considering that anaesthetics are typically administered in conjunction with pre-anaesthetic drugs, the increases in IOP induced by ketamine and isoflurane are not important, as the IOP did not exceed the baseline values. However, further studies are required to investigate these effects in patients with elevated IOP. 10.1002/vms3.1330

Effects of subcutaneous esketamine on blood pressure and heart rate in treatment-resistant depression. Del Sant Lorena Catarina,Sarin Luciana Maria,Magalhães Eduardo Jorge Muniz,Lucchese Ana Cecília,Tuena Marco Aurélio,Nakahira Carolina,Fava Victor Augusto Rodovalho,Delfino Rodrigo,Surjan Juliana,Steiglich Matheus Souza,Barbosa Matheus,Abdo Guilherme,Cohrs Frederico Molina,Liberatori Aroldo,Del Porto José Alberto,Lacerda Acioly Luiz Tavares,de Jesus Mari Jair Journal of psychopharmacology (Oxford, England) INTRODUCTION AND OBJECTIVES:The impact of multiple subcutaneous (s.c.) esketamine injections on the blood pressure (BP) and heart rate (HR) of patients with unipolar and bipolar treatment-resistant depression (TRD) is poorly understood. This study aimed to assess the cardiovascular safety of multiple s.c. doses of esketamine in patients with TRD. METHODS:Seventy TRD patients received 394 weekly s.c. esketamine injections in conjunction with oral antidepressant therapy for up to six weeks. Weekly esketamine doses were 0.5, 0.75 or 1.0 mg/kg according to each patient's response to treatment. Participants were monitored before each treatment and every 15 minutes thereafter for 120 minutes. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measurements for the entire treatment course. RESULTS:BP increased after the first s.c. esketamine injection, reaching maximum mean SBP/DBP levels of 4.87/5.54 mmHg within 30-45 minutes. At the end of monitoring, 120 minutes post dose, vital signs returned to pretreatment levels. We did not detect significant differences in BP between doses of 0.5, 0.75, and 1 mg/kg esketamine. Mean HR did not differ significantly between doses or before and after s.c. esketamine injection. CONCLUSIONS:The BP changes observed with repeated s.c. esketamine injections were mild and well tolerated for doses up to 1 mg/kg. The s.c. route is a simple and safe method of esketamine administration, even for patients with clinical comorbidities, including obesity, hypertension, diabetes, and dyslipidemia. However, 14/70 patients experienced treatment-emergent transient hypertension (SBP >180 mmHg and/or a DBP >110 mmHg). Therefore, we strongly recommend monitoring BP for 90 minutes after esketamine dosing. Since s.c. esketamine is cheap, requires less frequent dosing (once a week), and is a simpler procedure compared to intravenous infusions, it might have an impact on public health. 10.1177/0269881120922955

Low dose ketamine reduces pain perception and blood pressure, but not muscle sympathetic nerve activity, responses during a cold pressor test. Watso Joseph C,Huang Mu,Moralez Gilbert,Cramer Matthew N,Hendrix Joseph M,Cimino Frank A,Belval Luke N,Hinojosa-Laborde Carmen,Crandall Craig G The Journal of physiology KEY POINTS:Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans. ABSTRACT:Low dose ketamine is an effective analgesic medication. However, our knowledge of the effects of ketamine on autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low dose ketamine influences autonomic cardiovascular responses during painful stimuli in humans. We tested the hypothesis that low dose ketamine blunts perceived pain, and blunts subsequent sympathetic and cardiovascular responses during an experimental noxious stimulus. Twenty-two adults (10F/12M; 27 ± 6 years; 26 ± 3 kg m , mean ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed cold pressor tests (CPT; hand in ∼0.4°C ice bath for 2 min) pre- and 5 min post-drug administration (20 mg ketamine or saline). We compared pain perception (100 mm visual analogue scale), muscle sympathetic nerve activity (MSNA; microneurography, 12 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) during the pre- and post-drug CPTs separately using paired, two-tailed t tests. For the pre-drug CPT, perceived pain (P = 0.4378), MSNA burst frequency responses (P = 0.7375), and mean BP responses (P = 0.6457) were not different between trials. For the post-drug CPT, ketamine compared to placebo administration attenuated perceived pain (P < 0.0001) and mean BP responses (P = 0.0047), but did not attenuate MSNA burst frequency responses (P = 0.3662). Finally, during the post-drug CPT, there was a moderate relation between cardiac output and BP responses after placebo administration (r = 0.53, P = 0.0121), but this relation was effectively absent after ketamine administration (r = -0.12, P = 0.5885). These data suggest that low dose ketamine administration attenuates perceived pain and pressor, but not MSNA burst frequency, responses during a CPT. 10.1113/JP280706