PENYAKIT BRADYCARDIA

NAMA : RAHMI UTAMI

STAMBUK : 11020170024

Abstract
Many nociceptive, inflammatory, and neuropathic pathways contribute to perioperative pain.
Although opioids have long been a mainstay for perioperative analgesia, other non-opioid
therapies, and dexmedetomidine, in particular, have been increasingly used as part of a
multimodal analgesic regimen to provide improved pain control while minimizing opioid-related
side effects. This article reviews the evidence supporting the preoperative, intraoperative, and
postoperative efficacy of dexmedetomidine as an adjuvant, and the efficacy of intravenous,
spinal canal, and nerve block analgesia with dexmedetomidine for perioperative acute pain
treatment. While there have not been any large-scale clinical trials conducted, the current body of
evidence suggests that dexmedetomidine is suitable for use as an adjuvant analgesic at all
perioperative stages. However, there are potential adverse effects, such as hypotension and
bradycardia, which must be taken into consideration by clinicians.
(Bonnet et al., 2017)

Abstract
Rationale: Downregulation of the pacemaking ion channel, HCN4, and the corresponding ionic
current, If, underlies exercise training-induced sinus bradycardia in rodents. If this occurs in
humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes and it
will be important to understand the underlying processes. Objective: To test the role of HCN4 in
the training-induced bradycardia in human athletes and investigate the role of micro-RNAs
(miRs) in the repression of HCN4. Methods and Results: As in rodents, the intrinsic heart rate
was significantly lower in human athletes than non-athletes and in all subjects the rate-lowering
effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart
rate, consistent with HCN repression in athletes. Next generation sequencing and qPCR showed
remodelling of miRs in the sinus node of swim-trained mice. Computational predictions
highlighted a prominent role for miR-423-5p. Interaction between miR-423-5p and HCN4 was
confirmed by a dose-dependent reduction in HCN4 3'-UTR luciferase reporter activity on co-
transfection with precursor miR-423-5p (abolished by mutation of predicted recognition
elements). Knockdown of miR-423-5p with antimiR-423-5p reversed training-induced bradycardia
via rescue of HCN4 and If Further experiments showed that, in the sinus node of swim-trained
mice, upregulation of miR-423-5p (intronic miR) and its host gene, NSRP1, is driven by an
upregulation of the transcription factor Nkx2.5. Conclusions: HCN remodelling likely occurs in
human athletes as well as rodent models. miR-423-5p contributes to training-induced
bradycardia by targeting HCN4. This work presents the first evidence of miR control of HCN4
and heart rate. miR-423-5p could be a therapeutic target for pathological sinus node dysfunction
in veteran athletes.
(D'Souza et al., 2017)

Abstract
Haploinsufficiency of the melanocortin-4 receptor, the most common monogenetic obesity
syndrome in humans, is associated with a reduction in autonomic tone, bradycardia, and
incidence of obesity-associated hypertension. Thus, it has been assumed that melanocortin
obesity syndrome may be protective with respect to obesity-associated cardiovascular disease.
We show here that absence of the melanocortin-4 receptor (MC4R) in mice causes dilated
cardiomyopathy, characterized by reduced contractility and increased left ventricular diameter.
This cardiomyopathy is independent of obesity as weight matched diet induced obese mice do
not display systolic dysfunction. Mc4r cardiomyopathy is characterized by ultrastructural changes
in mitochondrial morphology and cardiomyocyte disorganization. Remarkably, testing of
myocardial tissue from Mc4r-/-mice exhibited increased ADP stimulated respiratory capacity.
However, this increase in respiration correlates with increased reactive oxygen species
production - a canonical mediator of tissue damage. Together this study identifies MC4R deletion
as a novel and potentially clinically important cause of heart failure.
(Litt et al., 2017)

Abstract
BACKGROUND:
Intraoperative nausea and vomiting (IONV) or postoperative nausea and vomiting (PONV)
affecting women undergoing regional anesthesia for cesarean section is an important clinical
problem since these techniques are used widely. There are burdens of literature about
IONV/PONV and several in parturient and cesarean. However, it needs more attention. The
underlying mechanisms of IONV and PONV in the obstetrical setting mainly include hypotension
due to sympathicolysis during neuraxial anesthesia, bradycardia owing to an increased vagal
tone, the visceral stimulation via the surgical procedure and intravenously administered opioids.
METHODS:
Given the high and even increasing rate of cesarean sections and the sparse information on the
etiology, incidence and severity of nausea and vomiting and the impact of prophylactic measures
on the incidence of PONV/IONV, this article aims to review the available information and provide
pragmatic suggestions on how to prevent nausea and vomiting in this patient cohort. Current
literature and guidelines were identified by electronic database searching (MEDLINE via PubMed
and Cochrane database of systematic reviews) up to present, searching through reference lists
of included literature and personal contact with experts.
DISCUSSION AND CONCLUSION:
Taking into account the current guidelines and literature as well as everyday clinical experience,
the first step for decreasing the incidence of IONV and PONV is a comprehensive management
of circulatory parameters. This management includes liberal perioperative fluid administration
and the application of vasopressors as the circumstances require. By using low-dose local
anesthetics, an additional application of intrathecal or spinal opioids or hyperbaric solutions for a
sufficient controllability of neuraxial distribution, maternal hypotension might be reduced.
Performing a combined spinal-epidural anesthesia or epidural anesthesia may be considered as
an alternative to spinal anesthesia. Antiemetic drugs may be administered restrainedly due to off-
label use in pregnant women for IONV or PONV prophylaxis and may be reserved for treatment.
(Jelting et al., 2017)

Abstract
Dexmedetomidine (Precedex) may be used as an alternative sedative in children, maintaining
spontaneous breathing, and avoiding tracheal intubation in a non-intubated moderate or deep
sedation (NI-MDS) approach. This open-label, single-arm, multicenter study evaluated the safety
of dexmedetomidine in a pediatric population receiving NI-MDS in an operating room or a
procedure room, with an intensivist or anesthesiologist in attendance, for elective diagnostic or
therapeutic procedures expected to take at least 30 min. The primary endpoint was incidence of
treatment-emergent adverse events (TEAEs). Patients received one of two doses dependent on
age: patients aged 28 weeks' gestational age to <1 month postnatal received dose level 1 (0.1
g/kg load; 0.05-0.2 g/kg/h infusion); those aged 1 month to <17 years received dose level 2 (1
g/kg load; 0.2-2.0 g/kg/h infusion). Sedation efficacy was assessed and defined as adequate
sedation for at least 80% of the time and successful completion of the procedure without the
need for rescue medication. In all, 91 patients were enrolled (dose level 1, n = 1; dose level
2, n = 90); of these, 90 received treatment and 82 completed the study. Eight patients in dose
level 2 discontinued treatment for the following reasons: early completion of diagnostic or
therapeutic procedure (n = 3); change in medical condition (need for intubation) requiring deeper
level of sedation (n = 2); adverse event (AE; hives and emesis), lack of efficacy, and physician
decision (patient not sedated enough to complete procedure; n = 1 each). Sixty-seven patients
experienced 147 TEAEs. The two most commonly reported AEs were respiratory depression
(bradypnea; reported per protocol-defined criteria, based on absolute respiratory rate values for
age or relative decrease of 30% from baseline) and hypotension. Four patients received
glycopyrrolate for bradycardia and seven patients received intravenous fluids for hypotension.
SpO2 dropped by 10% in two patients, but resolved without need for manual ventilation. All other
reported AEs were consistent with the known safety profile of dexmedetomidine. Two of the 78
patients in the efficacy-evaluable population met all sedation efficacy criteria. Dexmedetomidine
was well-tolerated in pediatric patients undergoing procedure-type sedation.
(Jooste et al., 2017)

Abstract
This study focused on the potential toxicity of silver nanoparticles (AgNPs) on cardiac
electrophysiology which is rarely investigated. We found that AgNPs (10-9-10-6g/ml)
concentration-dependently depolarized the resting potential, diminished the action potential, and
finally led to loss of excitability in mice cardiac papillary muscle cells in vitro. In cultured neonatal
mice cardiomyocytes, AgNPs (10-9-10-7g/ml) concentration-dependently decreased the
Na+ currents (INa), accelerated the activation, and delayed the inactivation and recovery of
Na+ channels from inactivation within 5min. AgNPs at 10-8g/ml also rapidly decreased the
inwardly rectifying K+ currents (IK1) and delayed the activation of IK1channels. Intravenous
injection of AgNPs at 3mg/kg only decreased the heart rate, while at 4mg/kg sequentially
induced sinus bradycardia, complete atrio-ventricular conduction block, and cardiac asystole.
AgNPs at 10-10-10-6g/ml did not increase reactive oxygen species (ROS) generation and only at
10-6g/ml mildly induced lactate dehydrogenase (LDH) release in the cardiomyocytes within 5min.
Endocytosis of AgNPs by cardiomyocytes was not observed within 5min, but was observed 1h
after exposing to AgNPs. Comparative Ag+ (0.02% of the AgNPs) could not induce above
toxicities. We conclude that AgNPs exert rapid toxic effects on myocardial electrophysiology and
induce lethal bradyarrhythmias. These acute toxicities are likely due to direct effects of AgNPs on
ion channels at the nano-scale level, but not caused by Ag+, ROS, and membrane injury. These
findings provide warning to the nanomedical practice using AgNPs.
(Lin et al., 2017)

Abstract
We report a case of symptomatic bradycardia caused by consumption of a Chinese herbal
medicine which was initially undisclosed to the attending emergency physician. The scientific
name of the herb is Panax japonicus. Electrocardiogram revealed sinus bradycardia. Laboratory
tests were normal except for the detection of a high serum digoxin level. Further interrogation of
the patient eventually disclosed ingestion of the herb which, however, did not contain any
digoxin. Other active ingredients in the herb include various types of ginsenoside. These are
digoxin-like substances that had caused the observed false-positive detection of digoxin by
fluorescence polarization immunoassay due to cross-reactivity. Our case-report provides an
important insight about a blind-spot in the field of laboratory medicine (clinical pathology),
namely, the false positive detection of digoxin due to crossreactivity in the immunoassay when
we come across digoxin-like substances in clinical scenarios, which has barely received attention
in the medical literature. It also conveys a clear educational message that with full understanding
of the laboratory methodology and its mechanistic rationale there are actually some tricks-of-the-
trade that allow us to optimize the specificity of the biochemical tests and the treatment of
digoxin-like substances overdose.
(Liu and Lee, 2017)

Abstract
OBJECTIVE:
Hypoxemic episodes commonly occur in very preterm infants and may be associated with
several adverse effects. Cerebral tissue oxygen saturation (StO2) as measured by near infrared
spectroscopy (NIRS) may be a useful measure to assess brain oxygenation. However,
knowledge on variability of StO2 is currently limited in preterm infants at this time, so StO2
dependency on arterial oxygenation (SpO2) and heart rate (HR) was assessed in preterm infants
using statistical methods of time series analysis.
STUDY DESIGN:
StO2, SpO2, and HR were recorded from 15 preterm infants every 2 seconds for six hours.
Statistical methods of time series and longitudinal data analysis were applied to the data.
RESULT:
The mean StO2 level was found as 72% (95% confidence interval (CI) 55.5% -85.5%) based on
a moving average process with a 5 minute order. Accordingly, longitudinal SpO2 measurements
showed a mean level of 91% (95% CI 69% -98%). Generally, compensation strategies to cope
with both StO2 and SpO2 desaturations were observed in the studied patients. SpO2 had a
significant effect on cerebral oxygenation (p<0.001), but HR did not, which led to inconclusive
results considering different time intervals.
CONCLUSION:
In infants with intermittent hypoxemia and bradycardia, we found a mean StO2 level of 72% and
a strong correlation with SpO2. We observed large differences between individuals in the ability
to maintain StO2 at a stable level.
(Mayer et al., 2017)

Abstract
Temporary parent vessel clip occlusion in aneurysm surgery is not always practical or feasible.
Adenosine-induced transient cardiac arrest may serve as an alternative. We retrospectively
reviewed our clinical database between September 2011 and July 2014. All patients who
underwent microsurgical clipping of intracranial aneurysms under adenosine-induced asystole
were included. A total of 18 craniotomies were performed, and 18 aneurysms were clipped under
adenosine-induced asystole (7 basilar arteries, 8 internal carotid arteries, 1 middle cerebral
artery, and 1 anterior communicating artery) in 16 patients (10 females, 6 males). Nine cases
were elective and seven after subarachnoid hemorrhage. Mean age was 54 years (range 39-70).
The indications for adenosine use were proximal control in narrow surgical corridors in 13 cases
and "aneurysm softening" in 4 cases. A single dose was used in 14 patients; 3 patients had
multiple boluses. The median (range) total dose was 30 (18-135) mg. Adenosine induced a
bradycardia with concomitant arterial hypotension in all patients, and the majority also had
asystole for 5-15 sec. Transient cardiac arrhythmias were noted in one patient (AFib in need of
electroconversion after two boluses). Nine clinical scenarios where adenosine-induced temporary
cardiac arrest and deep hypotension was an effective adjunct to temporary clipping during
microsurgical clipping of intracranial aneurysms were identified.
(Meling et al., 2017)

Abstract
OBJECTIVES:
To compare the efficacy and safety of endotracheal intubation (ETI) in a simulated clinical
environment in motion vs a motionless one.
MATERIAL AND METHODS:
Clinical simulation trial of ETI with 3 endotracheal tubes (Airtraq, Fast-trach, Macintosh
laryngoscope) in mannequins with realistic physiological responses (MetiMan) in 2 scenarios: an
environment in motion vs a motionless one. Thirty-six physicians expert in prehospital ETI
participated. Outcome variables were successful intubation, effective intubation, number of
attempts, maximum apnea time, and total maneuver time. The safety variables were the
presence of bradycardia, tachycardia, or high or low systolic blood pressures (ie, 20% variation
from baseline); hypoxemia (decrease in oxygen saturation to <90% or 10% below baseline), tube
placement in the esophagus or main bronchus, and dental trauma.
RESULTS:
No statistically significant differences between the 2 scenarios were found in the numbers of
successful ETI (motionless, 71 [65.7%]; in motion, 67 [62.0%]; P=.277) or effective ETI
(motionless, 104 [96.3%]; in motion, 105 [97.2%]; P=.108). Likewise, the number of attempts
were similar (motionless, 91 [84.2%]; in motion, 90 [83.3%]; P=.305). Nor did we see differences
in the mean (SD) maximum apnea times (motionless, 14.0 [5.6] seconds; in motion, 14.9 [8.1]
seconds; P=.570) or mean total maneuver times (motionless, 236.7 [73.4] seconds; in motion,
210.3 [77.9] seconds; P=.164). The prevalences of bradycardia, tachycardia, high or low systolic
blood pressure, hypoxemia, placements in the esophagus or bronchus, and dental trauma also
did not differ significantly between the 2 scenarios.
CONCLUSION:
Neither efficacy nor safety variables differed significantly when ETI was performed in
mannequins in a motionless environment vs one simulating ambulances in motion.
(Castejon de la Encina et al., 2017)
 DAFTAR PUSTAKA

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