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Topic:Romifidine

Romifidine is an alpha-2 adrenergic agonist used as a sedative and analgesic agent in horses. It acts on the central nervous system to produce sedation, muscle relaxation, and mild analgesia, making it useful for various veterinary procedures. Romifidine is often administered intravenously and has a dose-dependent effect, with the degree and duration of sedation varying based on the dosage. It can be used alone or in combination with other drugs to enhance its effects. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamics, pharmacokinetics, and clinical applications of romifidine in equine practice.
Influence of acepromazine on the cardiovascular effects of dobutamine in isoflurane-anaesthetised horses premedicated with romifidine.
Veterinary anaesthesia and analgesia    October 24, 2024   S1467-2987(24)00334-9 doi: 10.1016/j.vaa.2024.10.141
Wong AM, Schier MF, Hosgood G, Drynan E, Raisis AL.To explore the influence of acepromazine on the cardiovascular effects of dobutamine in isoflurane-anaesthetised horses premedicated with romifidine. Methods: Prospective randomised clinical trial. Methods: A total of 18 horses undergoing elective arthroscopy were enrolled, of which 12 horses requiring dobutamine were included. Methods: Horses were randomised to receive acepromazine 0.02 mg kg (Group A+) intravenously (IV) or none (Group A-), 35 minutes before anaesthesia. Horses received xylazine 0.2 mg kg concurrently to facilitate IV access. Horses were premedicated with romifidine 0.08 mg ...
Comparison of Detomidine or Romifidine in Combination with Morphine for Standing Magnetic Resonance Imaging in Horses.
Veterinary sciences    March 8, 2024   Volume 11, Issue 3 doi: 10.3390/vetsci11030124
Vullo C, Gugliandolo E, Biondi V, Biffarella M, Catone G, Tambella AM.The aim of this study was to determine the most appropriate sedation protocol for a standing magnetic resonance imaging (MRI) examination in horses, comparing continuous rate infusions (CRIs) of detomidine and romifidine combined with a single bolus of morphine. Sixteen horses referred for standing low-field open-magnet MRI were randomly assigned to one of two sedation protocols. The horses were premedicated with 0.03 mg/kg of intramuscular acepromazine, and those animals belonging to Group D received an intravenous (IV) loading dose of detomidine (0.01 mg/kg) 30 min later, while those of Grou...
Dobutamine use in horses during romifidine and isoflurane anaesthesia.
Research in veterinary science    December 22, 2023   Volume 167 105119 doi: 10.1016/j.rvsc.2023.105119
Ruíz-López P, Schauvliege S, Gasthuys F, Haspeslagh M.This retrospective study aimed to assess the incidence of hypotension and the subsequent administration of dobutamine in horses anesthetized with isoflurane and romifidine during elective surgery. Time from induction of anaesthesia to administration of dobutamine was registered, as well as the time and dose needed to restore mean arterial pressure (MAP) ≥ 70 mmHg. Additionally, the influence of patient and anaesthesia related parameters on the need for dobutamine supplementation was evaluated. In total, 118 horses were included in this retrospective study. Dobutamine was administered to e...
Evaluation of the agreement between lingual and thoracic limb noninvasive blood pressure with invasive blood pressure measurements in anaesthetized horses.
Veterinary anaesthesia and analgesia    August 16, 2023   Volume 51, Issue 1 1-9 doi: 10.1016/j.vaa.2023.08.007
Parra Martínez C, Rico Pérez B, Kaartinen J.To evaluate the agreement between noninvasive arterial blood pressure (NIBP) measured from the tongue and thoracic limb with invasive blood pressure (IBP), and to compare NIBP measured from the tongue and thoracic limb in anaesthetized horses. Methods: Prospective clinical study. Methods: A group of eight client-owned healthy horses anaesthetized for scheduled procedures, American Society of Anesthesiologists classification I-II, weighing (mean ± standard deviation) 498 ± 91 kg and aged 7.8 ± 6.75 years. Methods: Animals were premedicated with intravenous (IV) romifidine (0.04-0.08 mg kg-1)...
Effects of detomidine or romifidine during maintenance and recovery from isoflurane anaesthesia in horses.
Veterinary anaesthesia and analgesia    July 19, 2022   Volume 49, Issue 6 624-633 doi: 10.1016/j.vaa.2022.07.004
Alonso B, Carregaro A, Cuypers C, Michielsen A, Gasthuys F, Schauvliege S.To evaluate the effects of detomidine or romifidine on cardiovascular function, isoflurane requirements and recovery quality in horses undergoing isoflurane anaesthesia. Methods: Prospective, randomized, blinded, clinical study. Methods: A total of 63 healthy horses undergoing elective surgery during general anaesthesia. Methods: Horses were randomly allocated to three groups of 21 animals each. In group R, horses were given romifidine intravenously (IV) for premedication (80 μg kg), maintenance (40 μg kg hour) and before recovery (20 μg kg). In group D2.5, horses were given detomidine IV f...
Methadone or Butorphanol as Pre-Anaesthetic Agents Combined with Romifidine in Horses Undergoing Elective Surgery: Qualitative Assessment of Sedation and Induction.
Animals : an open access journal from MDPI    August 31, 2021   Volume 11, Issue 9 doi: 10.3390/ani11092572
Nannarone S, Giannettoni G, Laurenza C, Giontella A, Moretti G.While butorphanol is the most commonly used opioid in horses, methadone is not licensed in most countries. Our aim was to compare the effects of both drugs, combined with romifidine, regarding the quality of sedation and induction in horses undergoing elective surgery. Results indicate the suitability of both methadone and butorphanol in this patient population. Animals were scored 10 min after intravenous injection of sedatives. Despite lower overall sedation (OS) score in horses receiving methadone (p = 0.002), the quality and time of induction and intubation remained unchanged. None of the ...
Recovery Quality After Romifidine Versus Detomidine Infusion During Isoflurane Anesthesia in Horses.
Journal of equine veterinary science    September 3, 2020   Volume 94 103243 doi: 10.1016/j.jevs.2020.103243
Alonso BB, La Rosa L, Carregaro AB, Gasthuys F, Schauvliege S.To examine the influence of detomidine or romifidine on recovery quality from isoflurane anesthesia, 78 anesthetic records were reviewed, from horses that had received romifidine (group R) during premedication [80-120 μg kg IV], anesthetic maintenance (40 μg kg hour IV), and recovery (20 μg kg IV) or detomidine (group D), at doses of 10-20 μg kg IV, 5 μg kg hour IV, and 2.5 μg kg IV, respectively. Duration of the different recovery phases, the number of attempts to sternal and standing, scores for transition to standing (TrSta), balance and coordination once standing (BC), and fina...
Recovery quality following a single post-anaesthetic dose of dexmedetomidine or romifidine in sevoflurane anaesthetised horses.
Equine veterinary journal    February 21, 2020   Volume 52, Issue 5 685-691 doi: 10.1111/evj.13238
Hector RC, Rezende ML, Mama KR, Hess AM.Post-anaesthetic sedation is administered to horses to improve recovery quality from inhalant anaesthesia and reduce the risk of catastrophic injury. A single dose of dexmedetomidine for this purpose has not been evaluated clinically. Objective: To determine whether dexmedetomidine improves recovery quality from sevoflurane anaesthesia compared to a previously studied dose of romifidine. Methods: Prospective, randomised, masked clinical trial. Methods: Ninety-nine, adult, client-owned horses anaesthetised for elective procedures completed the trial. Anaesthetic protocol was standardised. Horse...
Recovery of horses from general anesthesia after induction with propofol and ketamine versus midazolam and ketamine.
Journal of the American Veterinary Medical Association    June 19, 2018   Volume 253, Issue 1 101-107 doi: 10.2460/javma.253.1.101
Jarrett MA, Bailey KM, Messenger KM, Prange T, Gaines B, Posner LP.OBJECTIVE To evaluate quality of recovery from general anesthesia in horses after induction with propofol and ketamine versus midazolam and ketamine. DESIGN Prospective randomized crossover study. ANIMALS 6 healthy adult horses. PROCEDURES Horses were premedicated with xylazine (1.0 mg/kg [0.45 mg/lb], IV), and general anesthesia was induced with midazolam (0.1 mg/kg [0.045 mg/lb], IV) or propofol (0.5 mg/kg [0.23 mg/lb], IV), followed by ketamine (3.0 mg/kg [1.36 mg/lb], IV). Horses were endotracheally intubated, and anesthesia was maintained with isoflurane. After 60 minutes, horses were giv...
The Modification and Performance of a Large Animal Anesthesia Machine (Tafonius®) in Order to Deliver Xenon to a Horse.
Frontiers in veterinary science    September 29, 2017   Volume 4 162 doi: 10.3389/fvets.2017.00162
Santangelo B, Robin A, Simpson K, Potier J, Guichardant M, Portier K.Xenon, due to its interesting anesthetic properties, could improve the quality of anesthesia protocols in horses despite its high price. This study aimed to modify and test an anesthesia machine capable of delivering xenon to a horse. Methods: An equine anesthesia machine (Tafonius, Vetronic Services Ltd., UK) was modified by including a T-connector in the valve block to introduce xenon, so that the xenon was pushed into the machine cylinder by the expired gases. A xenon analyzer was connected to the expiratory limb of the patient circuit. The operation of the machine was modeled and experimen...
Effect of detomidine or romifidine constant rate infusion on plasma lactate concentration and inhalant requirements during isoflurane anaesthesia in horses.
Veterinary anaesthesia and analgesia    March 30, 2017   Volume 44, Issue 3 473-482 doi: 10.1016/j.vaa.2016.01.002
Niimura Del Barrio MC, Bennett RC, Hughes JML.Influence of detomidine or romifidine constant rate infusion (CRI) on plasma lactate concentration and isoflurane requirements in horses undergoing elective surgery. Methods: Prospective, randomised, blinded, clinical trial. Methods: A total of 24 adult healthy horses. Methods: All horses were administered intramuscular acepromazine (0.02 mg kg) and either intravenous detomidine (0.02 mg kg) (group D), romifidine (0.08 mg kg) (group R) or xylazine (1.0 mg kg) (group C) prior to anaesthesia. Group D was administered detomidine CRI (10 μg kg hour) in lactated Ringer's solution (LRS), group...
Pharmacokinetics and pharmacodynamics of intravenous romifidine and propranolol administered alone or in combination for equine sedation.
Veterinary anaesthesia and analgesia    February 23, 2017   Volume 44, Issue 1 86-97 doi: 10.1111/vaa.12410
Cenani A, Brosnan RJ, Madigan S, Knych HK, Madigan JE.Propranolol has been suggested for anxiolysis in horses, but its sedation efficacy and side effects, both when administered alone and in combination with α-adrenoceptor agonists, remain undetermined. This study aimed to document the pharmacokinetics and pharmacodynamics of propranolol, romifidine and their combination. Methods: Randomized, crossover study. Methods: Six adult horses weighing 561 ± 48 kg. Methods: Propranolol (1 mg kg; treatment P), romifidine (0.1 mg kg; treatment R) or their combination (treatment PR) were administered intravenously with a minimum of 1 week between treatment...
Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability.
Equine veterinary journal    June 24, 2016   Volume 49, Issue 3 352-357 doi: 10.1111/evj.12590
Edmonds RE, Garvican ER, Smith RK, Dudhia J.To provide evidence to support recommendations regarding the co-administration of drugs with mesenchymal stem cell (MSC) therapy. Objective: To determine the influence of sedatives, local anaesthetic and corticosteroids on MSC viability and proliferation, in comparison to somatic cells derived from tendon (TDCs). Methods: In vitro cell culture. Methods: MSCs (n = 3) and TDCs (n = 2) were cultured in media containing a clinically relevant dose range of xylazine, romifidine, detomidine and butorphanol, mepivacaine, methylprednisolone, or triamcinolone acetonide. Cell viability in suspension cult...
Comparison of respiratory function during TIVA (romifidine, ketamine, midazolam) and isoflurane anaesthesia in spontaneously breathing ponies Part I: blood gas analysis and cardiorespiratory variables.
Veterinary anaesthesia and analgesia    August 7, 2014   Volume 41, Issue 6 583-591 doi: 10.1111/vaa.12167
Steblaj B, Schauvliege S, Pavlidou K, Gasthuys F, Savvas I, Duchateau L, Kowalczyk L, Moens Y.To compare pulmonary function and gas exchange in ponies during maintenance of anaesthesia with isoflurane or by a total intravenous anaesthesia (TIVA) technique. Methods: Experimental, cross-over study. Methods: Six healthy ponies weighing mean 286 (range 233-388) ± SD 61 kg, age 13 (9-16) ± 3 years. Methods: The ponies were anaesthetized twice, a minimum of two weeks apart. Following sedation with romifidine [80 μg kg(-1) intravenously (IV)], anaesthesia was induced IV with midazolam (0.06 mg kg(-1)) and ketamine (2.5 mg kg(-1), then maintained either with inhaled isoflurane (Fe'Iso = 1.1...
Effects of xylazine, romifidine, or detomidine on hematology, biochemistry, and splenic thickness in healthy horses.
The Canadian veterinary journal = La revue veterinaire canadienne    April 2, 2014   Volume 55, Issue 4 334-340 
Kullmann A, Sanz M, Fosgate GT, Saulez MN, Page PC, Rioja E.Alpha-2 agonist-induced changes in packed cell volume (PCV), total solids (TS), selected biochemical parameters, and splenic thickness were investigated in horses. Four healthy mares were treated in a blinded, randomized, cross-over design with a dose of xylazine (0.5 mg/kg), romifidine (0.04 mg/kg), or detomidine (0.01 mg/kg) IV, and detomidine (0.02 mg/kg) IM. Hematology, TS, colloid osmotic pressure (COP), plasma osmolality; glucose, lactate, urea (BUN) and electrolyte concentrations; venous blood pH and ultrasonographic splenic thickness were evaluated at intervals for 300 min. Repeated me...
Propofol with ketamine following sedation with xylazine for routine induction of general anaesthesia in horses.
The Veterinary record    November 11, 2013   Volume 173, Issue 22 550 doi: 10.1136/vr.101906
Posner LP, Kasten JI, Kata C.To document the suitability of intravenous propofol and ketamine following sedation with xylazine for routine anaesthetic induction in horses. Retrospective. 100 client-owned horses. Anaesthetic records were evaluated to determine: signalment, anaesthetic drug and dosages, need for additional induction agents, notation of any adverse events, duration of anaesthesia and recovery characteristics (rough or smooth, and rapid or prolonged). Horses were sedated with xylazine 0.99±(0.2) mg/kg intravenous and 23 horses were also administered butorphanol 0.02±(0.001) mg/kg intravenous. Horses were an...
[The effectiveness of romifidine on myocardial function in horses with and without heart disease, evaluated with M-mode echocardiography and PW-tissue Doppler imaging].
Berliner und Munchener tierarztliche Wochenschrift    November 10, 2013   Volume 126, Issue 9-10 436-443 
Nagel D, Gehlen H.The aim of this study was to evaluate to what extent the myocardial function in horses (measured by PW-tissue Doppler = PW-TDI) is affected during a sedation with romifidine (0.04 mg/kg, i. v.), particularly in case of an accompanying heart disease. Based on an echo- and electrocardiographic examination, a total of 45 horses was subdivided into group 1 (no heart disease), group 2 (heart disease without increased heart dimensions) and group 3 (heart disease with increased heart dimensions). Heart rate (HF), M-mode- (FS%) and TDI-measurements were performed before and after the application of ro...
Blood glucose, acid-base and electrolyte changes during loading doses of alpha₂-adrenergic agonists followed by constant rate infusions in horses.
Veterinary journal (London, England : 1997)    October 4, 2013   Volume 198, Issue 3 684-689 doi: 10.1016/j.tvjl.2013.09.063
Ringer SK, Schwarzwald CC, Portier K, Mauch J, Ritter A, Bettschart-Wolfensberger R.The aim of the present study was to investigate changes in blood glucose concentration ([Glu]B), acid-base status and electrolyte concentrations during constant rate infusions (CRI) of two alpha2-adrenergic agonists in seven horses treated in a blinded, randomised, crossover design with xylazine or romifidine. An intravenous (IV) bolus of xylazine (1mg/kg) or romifidine (80 μg/kg) was administered followed by an IV CRI of xylazine (0.69 mg/kg/h) or romifidine (30 μg/kg/h) for 2h. Blood samples were collected from the pulmonary artery before and after loading doses, during the CRI, and for 1h...
Prolonged anesthesia using sevoflurane, remifentanil and dexmedetomidine in a horse.
Veterinary anaesthesia and analgesia    May 29, 2013   Volume 40, Issue 5 521-526 doi: 10.1111/vaa.12048
Benmansour P, Duke-Novakovski T.A 10-year old Arabian mare had a slow-growing mass on the lower right mandible and required a large partial mandibulectomy. Methods: No abnormalities were detected apart from the mass. Results: A temporary tracheostomy was performed pre-operatively. Anesthesia was induced with xylazine followed by ketamine and diazepam. For 13 hours, anesthesia was maintained using sevoflurane, dexmedetomidine and remifentanil infusions, with the exception of surgical preparation time. Intra-operatively, ventilation was delivered through the cuffed tracheotomy tube. Heart and respiratory rates, ECG, arterial ...
Influence of drugs on the response characteristics of the LiDCO sensor: an in vitro study.
British journal of anaesthesia    November 19, 2012   Volume 110, Issue 2 305-310 doi: 10.1093/bja/aes380
Ambrisko TD, Kabes R, Moens Y.In a previous study, the authors found a large bias (50%) for lithium (LiDCO) compared with thermodilution cardiac output measurement methods in ponies receiving i.v. infusions of xylazine, ketamine, and midazolam. This prompted the authors to examine the effect of drugs on the LiDCO sensor. Methods: Drugs and lithium were dissolved in 0.9% saline to produce the following solutions: saline, saline-lithium, saline-drug, and saline-drug-lithium. The drug concentrations were overlapping the range of clinical interest as estimated from the published literature. These 38°C solutions were pumped th...
[Comparison of the effects of xylazine and romifidine administered perioperatively on the recovery of anesthetized horses].
The Canadian veterinary journal = La revue veterinaire canadienne    March 2, 2012   Volume 52, Issue 9 987-993 
Bauquier SH, Kona-Boun JJ.Comparison of the effects of xylazine and romifidine administered perioperatively on the recovery of anesthetized horses. The present study was designed to compare recoveries from anesthesia following the use of romifidine or xylazine in horses. In a prospective blind randomized clinical trial, 28 horses, undergoing elective arthroscopy, were randomly allocated into 2 groups. The intravenous anesthesia protocol used in the xylazine group was: butorphanol [0.02 mg/kg body weight (BW)] and xylazine (0.5 to 0.7 mg/kg BW) for premedication, diazepam (0.1 mg/kg BW) and ketamine (2.2 mg/kg BW) for i...
Effects of adding butorphanol to a balanced anaesthesia protocol during arthroscopic surgery in horses.
The Veterinary record    March 17, 2010   Volume 166, Issue 11 324-328 doi: 10.1136/vr.b4799
Caure S, Cousty M, Tricaud C.Three groups of horses scheduled for arthroscopic surgery were premedicated with 0.025 mg/kg acepromazine, 88 microg/kg romifidine and 25 mg/kg guaifenesin, and anaesthesia was induced with 2.2 mg/kg ketamine. In group 1 (14 horses), anaesthesia was maintained by halothane vaporised in oxygen, with supplementary doses of 20 microg/kg romifidine and 0.5 mg/kg ketamine every 20 minutes. The 17 horses in group 2 were maintained as for group 1; however, an additional dose of 0.05 mg/kg butorphanol was administered before the first incision. The 14 horses in group 3 were maintained as for group 2, ...
Effect of intratesticular injection of lidocaine on cardiovascular responses to castration in isoflurane-anesthetized stallions.
American journal of veterinary research    March 2, 2006   Volume 67, Issue 3 403-408 doi: 10.2460/ajvr.67.3.403
Haga HA, Lykkjen S, Revold T, Ranheim B.To evaluate the effect of intratesticular administration of lidocaine on cardiovascular responses and cremaster muscle tension during castration of isoflurane-anesthetized stallions. Methods: 28 healthy stallions (mean +/- SD age, 4.2 +/- 2.8 years) with no testicular abnormalities that were scheduled for castration. Methods: Each horse was given acepromazine (20 microg/kg, IM), romifidine (50 microg/kg, IV), and butorphanol (20 microg/kg, IV). Anesthesia was induced with ketamine (2.5 mg/kg, IV) and midazolam (50 microg/kg, IV) and maintained with isoflurane (1.7% end-tidal concentration). Af...
[Standing behavior in horses after inhalation anesthesia with isoflurane (Isoflo) and postanesthetic sedation with romifidine (Sedivet) or xylazine (Rompun)].
DTW. Deutsche tierarztliche Wochenschrift    July 18, 2003   Volume 110, Issue 6 244-248 
Bienert A, Bartmann CP, von Oppen T, Poppe C, Schiemann V, Deegen E.Isofluorane is a modern, only slightly depressive inhalation anaesthetic with excellent pharmacologic characteristics in use in equine medicine. In contrast to halothane, isofluorane is hardly broken down in the liver, but is eliminated by the lung. It low solubility in blood permits excellent control of anaesthesia. However, due to its swift elimination from the organism there is heightened risk of premature recovery from isofluorane anaesthesia. In this study the recovery phases of 96 horses were monitored for its duration and the animals' physical coordination. The horses were divided into ...
Comparison of detomidine and romifidine as premedicants before ketamine and halothane anesthesia in horses undergoing elective surgery.
American journal of veterinary research    March 30, 2001   Volume 62, Issue 3 359-363 doi: 10.2460/ajvr.2001.62.359
Taylor PM, Bennett RC, Brearley JC, Luna SP, Johnson CB.To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. Methods: 100 client-owned horses. Methods: After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. Results: Mean (+/- SD) d...
A comparison of romifidine and xylazine when used with diazepam/ketamine for short duration anesthesia in the horse.
The Canadian veterinary journal = La revue veterinaire canadienne    October 1, 1996   Volume 37, Issue 10 601-609 
Kerr CL, McDonell WN, Young SS.The purpose of this study was to compare and evaluate sedation with intravenous xylazine (1.1 mg/kg bodyweight [BW]) versus intravenous romifidine (100 micrograms/kg BW) followed by induction of anesthesia with intravenous diazepam (0.04 mg/kg BW) and ketamine (2.2 mg/kg BW). Twelve healthy horses were used in a blinded, randomized, cross-over design. Heart rate, presence of 2nd degree atrioventricular heart blocks (2 degrees AVB), respiratory rate, arterial blood pressures, blood gases, packed cell volume, total serum proteins, and duration of anesthesia and recumbency were recorded. Inductio...
Effects of additional premedication on romifidine and ketamine anaesthesia in horses.
Acta veterinaria Scandinavica    January 1, 1996   Volume 37, Issue 3 315-325 doi: 10.1186/BF03548097
Marntell S, Nyman G.The clinical and cardiorespiratory effects of premedication with acepromazine, butorphanol or diazepam in addition to romifidine before induction of anaesthesia with ketamine were studied in 6 horses on 4 random occasions. Administration of romifidine alone or in combination with butorphanol resulted in an increase in arterial blood pressure, accompanied by a significant decrease in heart rate with second-degree atrio-ventricular heart block. Induction of anaesthesia with ketamine returned the heart rate to baseline value, but the arterial blood pressure was significantly increased compared to...
A preliminary study on the effects of atropine sulphate on bradycardia and heart blocks during romifidine sedation in the horse.
Veterinary research communications    January 1, 1990   Volume 14, Issue 6 489-502 doi: 10.1007/BF00367061
Gasthuys F, Parmentier D, Goossens L, De Moor A.Romifidine (STH 2130-Cl or Sedivet) is an alpha 2-agonistic imino-imidazol sedative for intravenous use in horses recently developed by Boehringer Ingelheim, Vetmedica GmbH. An exploratory study was done in nine warm-blood horses, randomly divided into three groups, which received different dosages of romifidine (0.04, 0.08 and 0.12 mg/kg of body weight (BWT) intravenously (i.v.)) with at least one week's interval between tests. Romifidine induced a marked bradycardia accompanied by second degree atrioventricular (AV) block and some sinus blocks at all tested dosages. A placebo (NaCl 0.9% i.v....