Dexmedetomidine Use in Patients with 33oC Targeted Temperature Management: Focus on Bradycardia as an Adverse Effect

Hyo-yeon Seo,Byoung-joon Oh,Eun-jung Park,Young-gi Min,Sang-cheon Choi 대한중환자의학회 2015 Acute and Critical Care Vol.30 No.4

Background: This study aimed to investigate bradycardia as an adverse effect after administration of dexmedetomidine during 33oC target temperature management. Methods: A retrospective study was conducted on patients who underwent 33oC target temperature management in the emergency department during a 49-month study period. We collected data including age, sex, weight, diagnosis, bradycardia occurrence, target temperature management duration, sedative drug, and several clinical and laboratory results. We conducted logistic regression for an analysis of factors associated with bradycardia. Results: A total of 68 patients were selected. Among them, 39 (57.4%) showed bradycardia, and 56 (82.4%) were treated with dexmedetomidine. The odds ratio for bradycardia in the carbon monoxide poisoning group compared to the cardiac arrest group and in patients with higher body weight were 7.448 (95% confidence interval [CI] 1.834-30.244, p = 0.005) and 1.058 (95% CI 1.002-1.123, p = 0.044), respectively. In the bradycardia with dexmedetomidine group, the infusion rate of dexmedetomidine was 0.41 ± 0.15 μg/kg/ h. Decisions of charged doctor’s were 1) slowing infusion rate and 2) stopping infusion or administering atropine for bradycardia. No cases required cardiac pacing or worsened to asystole. Conclusions: Despite the frequent occurrence of bradycardia after administration of dexmedetomidine during 33oC target temperature management, bradycardia was completely recovered after reducing infusion rate or stopping infusion. However, reducing the infusion rate of dexmedetomidine lower than the standard maintenance dose could be necessary to prevent bradycardia from developing in patients with higher body weight or carbon monoxide poisoning during 33oC targeted temperature management.

Effectiveness of Bradycardia as a Single Parameter in the Pediatric Acute Response System

최유현,이현승,이봉진,서동인,박준동 대한중환자의학회 2014 Acute and Critical Care Vol.29 No.4

Background: Various tools for the acute response system (ARS) predict and prevent acute deterioration in pediatric patients. However, detailed criteria have not been clarified. Thus we evaluated the effectiveness of bradycardia as a single parameter in pediatric ARS. Methods: This retrospective study included patients who had visited a tertiary care children’s hospital from January 2012 to June 2013, in whom ARS was activated because of bradycardia. Patient’s medical records were reviewed for clinical characteristics, cardiologic evaluations, and reversible causes that affect heart rate. Results: Of 271 cases, 261 (96%) had ARS activation by bradycardia alone with favorable outcomes. Evaluations and interventions were performed in 165 (64.5%) and 13 cases (6.6%) respectively. All patients in whom ARS was activated owing to bradycardia and another criteria underwent evaluation, unlike those with bradycardia alone (100.0% vs. 63.2%, p = 0.016). Electrocardiograms were evaluated in 233 (86%) cases: arrhythmias were due to borderline QT prolongation and atrioventricular block (1st and 2nd-degree) in 25 cases (9.2%). Bradycardia-related causes were reversible in 202 patients (74.5%). Specific causes were different in departments at admission. Patients admitted to the hemato-oncology department required ARS activation during the night (69.3%, p = 0.03), those to the endocrinology department required ARS activation because of medication (72.4%, p < 0.001), and those to the gastroenterology department had low body mass indexes (32%, p = 0.01). Conclusions: Using bradycardia alone in pediatric ARS is not useful, because of its low specificity and poor predictive ability for deterioration. However, bradycardia can be applied to ARS concurrently with other parameters.

Preoperative dexmedetomidine and intraoperative bradycardia in laparoscopic cholecystectomy: a meta-analysis with trial sequential analysis

De Cassai Alessandro,Sella Nicolò,Geraldini Federico,Zarantonello Francesco,Pettenuzzo Tommaso,Pasin Laura,Iuzzolino Margherita,Rossini Nicolò,Pesenti Elisa,Zecchino Giovanni,Munari Marina,Navalesi Pa 대한마취통증의학회 2022 Korean Journal of Anesthesiology Vol.75 No.3

Background: While laparoscopic surgical procedures have various advantages over traditional open techniques, artificial pneumoperitoneum is associated with severe bradycardia and cardiac arrest. Dexmedetomidine, an imidazole derivative that selectively binds to α2-receptors and has sedative and analgesic properties, can cause hypotension and bradycardia. Our primary aim was to assess the association between dexmedetomidine use and intraoperative bradycardia during laparoscopic cholecystectomy. Methods: We performed a systematic review with a meta-analysis and trial sequential analysis using the following PICOS: adult patients undergoing endotracheal intubation for laparoscopic cholecystectomy (P); intravenous dexmedetomidine before tracheal intubation (I); no intervention or placebo administration (C); intraoperative bradycardia (primary outcome), intraoperative hypotension, hemodynamics at intubation (systolic blood pressure, mean arterial pressure, heart rate), dose needed for induction of anesthesia, total anesthesia requirements (both hypnotics and opioids) throughout the procedure, and percentage of patients requiring postoperative analgesics and experiencing postoperative nausea and vomiting and/or shivering (O); randomized controlled trials (S). Results: Fifteen studies were included in the meta-analysis (980 patients). Compared to patients that did not receive dexmedetomidine, those who did had a higher risk of developing intraoperative bradycardia (RR: 2.81, 95% CI [1.34, 5.91]) and hypotension (1.66 [0.92,2.98]); however, they required a lower dose of intraoperative anesthetics and had a lower incidence of postoperative nausea and vomiting. In the trial sequential analysis for bradycardia, the cumulative z-score crossed the monitoring boundary for harm at the tenth trial.Conclusions: Patients undergoing laparoscopic cholecystectomy who receive dexmedetomidine during tracheal intubation are more likely to develop intraoperative bradycardia and hypotension.

Dose fentanyl injection for blunting the hemodynamic response to intubation increase the risk of reflex bradycardia during major abdominal surgery?

김진경,박정민,이철희,김덕경 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.63 No.5

Background: Although supplemental fentanyl has been widely used to blunt the hemodynamic responses to laryngoscopic intubation, its residual vagotonic effect may increase the risk of reflex bradycardia. We compared the incidence and severity of significant reflex bradycardia after a bolus injection of equivalent doses of fentanyl and remifentanil (control drug). Methods: In this prospective, randomized, double-blind study, 220 adult patients undergoing major abdominal surgery were randomly assigned to receive fentanyl (1.5 μg/kg) or remifentanil (1.5 μg/kg). No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to < 50beats per minute (bpm) or to 50-59 bpm associated with a systolic arterial pressure < 70 mmHg in connection with surgical maneuvers. If bradycardia or hypotension developed, atropine or ephedrine was administered following a predefined treatment protocol. Results: In total, 188 subjects (remifentanil, 95; fentanyl, 93) were included. The proportion of subjects with symptomatic reflex bradycardia in the fentanyl group was similar to that in the remifentanil group (30.1% vs. 28.4%,respectively). Atropine and/or ephedrine were needed similarly in both groups. The differences between the group of 55 patients who presented with symptomatic reflex bradycardia were not statistically significant with respect to the lowest heart rate, anesthetic depth-related data (bispectral index and end-tidal sevoflurane concentration), or the proportion of causative surgical maneuvers. Conclusions: Fentanyl (1.5 μg/kg) administered intravenously during anesthetic induction is unlikely to increase the incidence and severity of significant reflex bradycardia in patients undergoing major abdominal surgery.

서맥으로 치료받은 만성 신질환 환자들에 대한 임상적 고찰

최두환 ( Choe Du Hwan ),안선호 ( An Seon Ho ),정성원 ( Jeong Seong Won ),이유민 ( Lee Yu Min ),김현정 ( Kim Hyeon Jeong ),이명수 ( Lee Myeong Su ),백승훈 ( Baeg Seung Hun ),송주흥 ( Song Ju Heung ) 대한신장학회 2004 Kidney Research and Clinical Practice Vol.23 No.2

배 경 : 만성 신질환 환자들은 심혈관계 합병증으로 인한 사망률이 증가하는데 고칼륨혈증 등과 같은 전해질 이상을 동반할 수 있고, 기저질환 혹은 약물에 의해서도 변화될 수 있어 주의가 요구된다. 저자들은 현저한 서맥으로 인한 증상을 주소로 내원한 만성 신질환 환자들의 임상적 특징을 관찰하고 심전도 변화를 야기하는 요인들의 분석과 항께 안정적으로 투석을 시행할 수 있는 방법을 제시하고자 한다. 방 법 : 1999년 7월부터 2003년 7월까지 서맥 때문에 응급실로 내원한 만성 신질환 환자에서 서맥의 조절 및 고칼륨혈증에 대한 통상적인 방법을 시행했음에도 불구하고 생명징후의 불안정과 임상적 증상이 지속되어 임시 인공 심박조율기를 삽입한 후 혈액투석을 시행한 14예에 대한 임상적 특성과 유발 요인을 관찰하였다. 결 과 : 관찰 대상 14예 중 유지혈액투석 중인 말기신부전은 8예, 투석전 만성 신질환 환자는 6예였다. 만성 신질환 원인은 당뇨병성이 10예, 비당뇨병성이 4예였고, 평균 연령은 60.8±11.4세, 10명은 남자, 4명은 여자였다. 응급실 내원시 검사실 소견은 s-Cr 8.2±4.1 ㎎/dL, K 6.0±1.4 mEq/L, Ca²^(+) 4.4±1.3 ㎎/dL, P 5.7±3.4 ㎎/dL, Mg 3.2±0.8 ㎎/dL, HCO₃^(-) 16.4土3,7 mEq/L, 수축기 혈압 95.7±19.9 mmHg, 심박동 26.5±6.6 bpm였다. 심 전도 소견은 방실접합부 이탈율동 (sinus arrest with escape junctional rhythm) 11예, 완전 3도 방실전도장애 (complete third degree atrioventricular disturbance) 3예였다. 이중 방실접합부 이탈율동이었던 11예는 임시 인공심박조율기를 삽입하고 혈액투석을 시행한 후 정상 율동으로 회복되었고, 유지혈액투석 중이던 환자에서 발생한 완치 3도 방실전도장에 1예는 영구형 인공심박 조율기를 삽입하였으나 6개월 후 정상 율동으로 회복되었다. 투석 전인 만성 신질환 환자에서 발생한 완전 3도 방실전도장애 2예 중, 1예는 주석 후 정상 율동으로 회복되었고 1예는 투석 후에도 정상 율동으로 회복되지 않아 영구형 인공 심박조율기를 삽입한 후 현재까지 작동 중이다. 혈중 칼륨이 6.5 mEq/L 미만인 경우가 9예었고, 5.5 mEq/L 미만인 경우도 4예가 있었으며 이들은 모두 당뇨를 기저질환으로 가지고 있으면서 4예 모두 digoxin을 사용하고 있었고 diltiazem은 3예, α,β-차단제는 1예에서 사용하고 있었다. 또한 전체 14예 중 8예에서 diltiazem, 3예에서 β-차단제, 3예에서 α,β-차단제를 사용하고 있었고, 1예에서는 미상의 항고혈압제를 사용하였다. Digoxin은 5예에서 사용 중이었고 이중 4예는 정상범주의 농도를 유지하고 있었고 1예에서 4.0 ng/mL였다. 투석 전인 만성 신질환 환자군과 유지혈액투석 중인 환자군으로 구분 하여 비교시 K 5.8土1.0 vs 6.2±1.7 mEq/L, HCO₃^(-) 17.7±3.7 vs 15.4±3.8 mEq/L, Ca²^(+) 4.5±2.3 vs 4.3±0.6 ㎎/dL로 통계적인 유의성은 없었고, Mg만 2.4±0.9 vs 3.5±0.5 ㎎/dL (p<0.05)로 통계적 유의성이 있었다. 결 론 : 만성 신질환 환자에서 서맥이 발생할 수도 있으며, 특히 당뇨가 합병된 경우 diltiazem, digoxin, β-차단제, α,β-차단제 등과 같이 전도장애를 야기할 수 있는 약물은 주의해서 사용해야 하며, 고칼륨혈증이 발생되지 않도록 해야 한다. 뿐만 아니라 고칼륨혈증이 없더라고 요독증 때문에도 서맥이 발생할 수 있음으로 보존적 치료에도 생명징후가 불안정한 경우 우선적으로 임시 인공심박조율기를 사용해 혈압을 안정화시킨 후 가급적 빨리 혈액투석을 시행하는 것이 치료의 한 방법이라 사료된다. Since profound hyperkalemia induces fatal arrhythmias, the recognition of its electrocardiographic manifestations is very important. The changes on the ECG correlated roughly with the severity of hyperkalemia. It has been, however, less recognized that severe hyperkalemia is associated with bradycardia. We present 14 patients with chronic kidney disease manifesting marked bradycardia in the presence or absence of hyperkalemia. It is interesting that diabetes mellitus which was complicated in 10 of 14 patients in the present study might exaggerate bradycardia with or without hyperkalemla. 9 patients, who were taking drugs such as diltiazem. β-blocker, α, β-blocker, and digoxin, developed bradycardia even when their plasma potassium concentration were moderate (<6.5 mEq/L). Therefore, we suggest that synergistic action of these drugs, hyperkalemia, diabetse mellitus, and uremic toxin in patient with chronic kidney disease might play a role in inducing bradycardia. (Korean J Nephrol 2004;23(2):256-262)

Dexmedetomidine을 투여한 내과중환자실 환자의 심혈관계 부작용 발생률과 위험인자 분석

안혜림,김지원,안서현,박애령,황보신이 한국병원약사회 2020 병원약사회지 Vol.37 No.3

Background : Dexmedetomidine is a selective α2 agonist with sedative, analgesic, and sympatholytic properties. Dexmedetomidine has cardiovascular risks such as hypotension and bradycardia. For this reason, the U.S. Food and Drug Administration (FDA) recommends the short-term use of dexmedetomidine less than 24 hours. Therefore, this study was aimed at analyzing the current status and risk factors of the cardiovascular side effects of dexmedetomidine. Methods : A retrospective chart review of all adult critically ill patients in the medical intensive care units who received dexmedetomidine from January 2016 to May 2017 was performed. The incidence, risk factors and prognosis of the cardiovascular adverse effects were analyzed. Results : The total number of patients was 135, and the mean hours of dexmedetomidine administration was 165 hours. A total of 102 patients (75.6%) developed cardiovascular side effects. Among them, hypotension occurred in 99 patients (73.3%), of which 53 patients (53.5%) developed hypotension within 24 hours. Bradycardia occurred in eight patients (5.9%), of which two patients (25.0%) developed bradycardia within 24 hours. Multivariate analysis of the risk factors for hypotension showed an association between hypotension and low baseline mean arterial pressure (MAP)(p=0.028), patients with acute respiratory distress syndrome (ARDS)(p=0.030) and those given norepinephrine (p=0.017). The incidence of hypotension was lower in patients with underlying hypertension (p=0.030). Univariate analysis of the risk factors for bradycardia showed that the incidence of bradycardia was higher in patients with lower baseline heart rates (p=0.033), higher body weight (p=0.008), and those undergoing hemodialysis (p=0.009). Also, there were no significant differences in the days of mechanical ventilation, the number of hospital days, and the mortality rate in patients with hypotension or bradycardia. Conclusion : Dexmedetomidine was associated with a higher incidence of cardiovascular side effects. Specifically, patients who were diagnosed with lower MAP, ARDS, or in combination with norepinephrine use were more likely to develop hypotension. Therefore, it is necessary to closely monitor cardiovascular adverse effects in patients with these risk factors.

The effect of beta-blockers in acute heart failure according to heart rate

( Hyun-jin Kim ),( Sang-ho Jo ),( Min-ho Lee ),( Won-woo Seo ),( Jin-oh Choi ),( Kyu-hyung Ryu ) 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.4

Background/Aims: Beta-blockers (BBs) have been shown to improve clinical outcomes in heart failure (HF) patients. We evaluated the prescribing status of BBs in patients with HF with reduced ejection fraction (HFrEF) at discharge according to the presence or not of bradycardia, and its effect on prognosis. Methods: Study data were obtained from a multicenter cohort of 3,200 patients hospitalized for HF. Patients were classified into four groups according to the presence of bradycardia and use of BBs at discharge. The primary outcome was the incidence of all-cause death during follow-up. Results: Of 1,584 patients with HFrEF, 281 patients died during follow-up (median 523 days, mean 578.5 ± 429.7 days). In patients with bradycardia, the all-cause death rate did not significantly differ according to the use of BBs, but in those patients without bradycardia, the incidence of all-cause death was significantly lower in the BBs group than the no BBs group. Among these four groups, patients with heart rate (HR) ≥ 60 beats/min with no BBs group had the lowest cumulative death-free survival rate. In addition, HR ≥ 60 beats/min with BBs use was independently associated with a 31% reduced risk of all-cause death in patients with HFrEF. Conclusions: BBs had a beneficial effect on clinical prognosis only in those HFrEF patients without bradycardia. Therefore, BBs should be given by clinicians to HF patients without bradycardia to improve their clinical outcomes.

증례보고 : 비디오 흉강경 수술 후 수술 부위의 생리식염수 세척에 의해 발생한 동성서맥

박상진 ( Sang Jin Park ),이동원 ( Dong Won Lee ) 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.57 No.2

A 43-year-old man underwent lipoma excision operation with video-assisted thoracoscopic surgery (VATS). Upon completion of the surgery, 20℃ cold saline irrigation was performed to clean the surgical field. During this procedure, a sudden sinus bradycardia (33 beats/min) occurred. After interruption of the irrigation, the normal sinus rhythm returned spontaneously. With the suspicion that the cold saline could have induced the bradycardia, 40℃ warm saline irrigation was performed; however, the repeat sinus bradycardia occurred again. The saline irrigation was stopped and the heart rate returned to normal. We conclude that although warm saline irrigation is a common practice after surgical procedures to ensure hemostasis and to clean the surgical field, it may induce profound sinus bradycardia. (Korean J Anesthesiol 2009;57:233∼6)

Synergistic Restoring Effects of Isoproterenol and Magnesium on KCNQ1-Inhibited Bradycardia Cell Models Cultured in Microelectrode Array

Kim, Sook Kyoung,Pak, Hui-Nam,Park, Yongdoo S. Karger AG 2014 Cardiology Vol.128 No.1

<P>Abstract</P><P><B><I>Objectives:</I></B> Bradycardia is caused by loss-of-function mutations in potassium channels that regulate phase 3 repolarization of the cardiac action potential. The purpose of this study is to monitor the effects of potassium channel (KCNQ1) inhibition and to evaluate the effects of isoproterenol (ISO) and MgSO<SUB>4</SUB> in restoring sinus rhythm in atrial cells. <B><I>Methods:</I></B> Microelectrode array was used to analyze conduction velocity, voltage amplitude and cycle length of atrial cells (HL-1). A combination of ISO and MgSO<SUB>4</SUB> was used to restore sinus rhythm in these cells. <B><I>Results:</I></B> mRNA expression levels of KCNQ1 (42.2 vs. 100%, p < 0.0001), connexin 43 (29.6 vs. 100%, p = 0.0033), atrial natriuretic peptide (31.0 vs. 100%, p = 0.0030), cardiac actin (38.2 vs. 100%, p < 0.0001) and α-myosin heavy chain (31.2 vs. 100%, p = 0.00254) were significantly lower in the KCNQ1 gene-inhibited group compared to the control group. When treated with MgSO<SUB>4</SUB> (1 m<smlcap>M</smlcap>) and ISO (10 μ<smlcap>M</smlcap>), conduction velocity (0.0208 ± 0.0036 vs. 0.0086 ± 0.0014 m/s, p = 0.0004) and voltage amplitude (1,210.78 ± 65.81 vs. 124.1 ± 13.30 μV, p < 0.0001) were higher, and cycle length (431.55 ± 2.05 vs. 1,015.15 ± 4.31 ms, p < 0.0001) was shorter than in the gene-inhibited group. <B><I>Conclusion:</I></B> Inhibition of sinus rhythm in the bradycardia cell model was recovered by treatment with ISO and MgSO<SUB>4</SUB>, demonstrating the potency of combination therapy in the treatment of bradycardia.</P><P>© 2014 S. Karger AG, Basel</P>

Fluid loading during spinal anesthesia can reduce bradycardia after intravenous dexmedetomidine infusion

임세훈,이원진,한용재,문성호,조광래,김명훈 대한마취통증의학회 2019 Anesthesia and pain medicine Vol.14 No.1

Background: Dexmedetomidine has been widely used during spinal anesthesia to provide sedation. However, dexmedetomidine frequently causes significant bradycardia. This study was designed to evaluate whether fluid loading could reduce the incidence of bradycardia after intravenous dexmedetomidine infusion in patients under spinal anesthesia. Methods: A total of 99 patients, 18 to 65 years of age, with American Society of Anesthesiologists physical status 1 or 2, who were scheduled for elective total knee replacement or internal fixation of lower leg fracture under spinal anesthesia were enrolled. The patients were randomly assigned into one of the three groups, and fluid was loaded as follows: group LOW - 4 ml/kg, group MID - 8 ml/kg, and group HI - 12 ml/kg. After fluid loading and spinal anesthesia, dexmedetomidine was infused as follows: 1 μg/kg of loading dose for 10 minutes, thereafter continuous infusion at 0.4 μg/kg/h. Results: The heart rate of group HI was significantly higher than that of group LOW (P = 0.049). The dosage of atropine administration was significantly lower in group HI than in group LOW (P = 0.003). The change in thoracic fluid contents was significantly higher in group HI than in group LOW (P = 0.018). Conclusions: Fluid loading during spinal anesthesia can reduce the incidence and extent of bradycardia after intravenous dexmedetomidine infusion.