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Abstract Tachycardia is a key compensatory mechanism in septic shock. Many patients, however, develop refractory tachycardia, which persists despite correction of hypovolaemia with fluids and vasopressors. This may be the result of excessive sympathetic stimulation from endogenous and exogenous sources, or due to the direct effect of bacterial endotoxins and inflammatory mediators on the sinoatrial node (SAN). Evidence suggests that persistent tachycardia may be harmful for patients with septic shock. Ivabradine is the first cardiac pacemaker current (funny current) inhibitor that lowers heart rate without any negative effect on cardiac conductivity or contractility. Ivabradine has been evaluated for heart rate control in patients with acute decompensated heart failure and cardiogenic shock, with promising results. Ivabradine is a cardiotonic agent used for the symptomatic management of angina pectoris. It is taken orally or crushed then injected through a nasogastric tube twice daily. Ivabradine was approved by the European Medicines Agency in 2005. Some preliminary findings suggest that ivabradine may be useful in the management of patients with septic shock. Thus, this study aimed to evaluate the effect of the cardiac pacemaker current inhibitor ivabradine on heart rate and outcome in patients with septic shock. To elucidate our aim a prospective, single blinded randomized controlled clinical trial study conducted on 102 of septic shock patients who was non-randomly selected and this study was carried out in Intensive Care department Benha University. The period was 9 months from June 2022 to February 2023. Our patients were divided into two groups: Case group: septic shock patients were treated with ivabradine (dose of 5 mg /12 hrs) orally or crushed then infused through nasogastric tube beside regular management. Control group: septic shock patients were treated with regular management without using ivabradine. All patients were subjected to the following: Full history taking including: Age and Sex. Medical history including diabetes mellitus, hypertension, chronic kidney disease, ischemic heart disease, urinary tract infection, central nervous system and Pneumonia. Vital Signs including Pulse (Heart rate, volume: A low volume pulse indicates dehydration, character: A fast but weak pulse depicts shock). The results of this study could be summarized as follow: ● There was no significant difference among the studied groups regarding APACHE II (P=0.674). While, Sequential organ failure assessment at 1st, 4th and 7th were significantly decreased among ivabradine group (11.96±2.34, 9.84±2.91, 7.69±4.61) than control group (13.00±1.47, 13.04±4.15, 12.84±6.90) respectively, (P<0.05). ● Mean arterial pressure at 1st was significantly decreased among the ivabradine group (66.41±2.96) than the control group (68.52±3.53), (P=0.001). While, there was no significant difference among the studied groups regarding mean arterial pressure at 4th and 7th (P>0.05). Furthermore, heart rate at 1st, 4th and 7th were significantly decreased among ivabradine group (126.43±3.81, 100.67±5.11, 83.48±5.33) than control group (127.75±2.30, 115.93±2.84, 108.57±4.51) respectively, (P<0.05). Additionally, NE at 1st, 4th and 7th were significantly decreased among ivabradine group (0.24±0.08, 0.08±0.13, 0.05±0.14) than control group (0.30±0.04, 0.16±0.15, |