Oral Albuterol Treatment in Three Pediatric Patients with Bradycardia: A Novel Therapy.

Clinically significant bradycardia is an uncommon problem in children, but one that can cause significant morbidity and sometimes necessitates implantation of a pacemaker. The most common causes of bradycardia are complete heart block (CHB), which can be congenital or acquired, and sinus node dysfunction, which is rare in children with structurally normal hearts. Pacemaker is indicated as therapy for the majority of children with CHB, and while early mortality is lower in postnatally diagnosed CHB than in fetal CHB, it is still up to 16%. In young children, less invasive transvenous pacemaker systems can be technically challenging to place and carry a high risk of complications, often necessitating surgical epicardial pacemaker placement, which usually entails a median sternotomy. We report three cases of pediatric patients referred for pacemaker implantation for different types of bradycardia, treated at our institution with oral albuterol with therapeutic results that avoided the need for surgical pacemaker implantation at that time.

Effect of Dexmedetomidine on Intraoperative Hemodynamics and Blood Loss in Patients Undergoing Spine Surgery: A Systematic Review and Meta-Analysis.

Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 - 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 - 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 - 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 - 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 - 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 - 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 - 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 - 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 - 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95%CI: -109.04 - -56.90; P<0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

High-dose IV magnesium in mesothelioma patients receiving surgery with hyperthermic intraoperative cisplatin: Pilot studies and design of a phase II randomized clinical trial.

INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.

Retrospective evaluation of ketamine versus droperidol on time to restraint removal in agitated emergency department patients.

PURPOSE: Acute agitation and violent behavior in the emergency department (ED) can lead to significant patient morbidity and contribute to the growing problem of workplace violence against health care providers. To our knowledge, there is no available literature directly comparing intramuscular ketamine to intramuscular droperidol in ED patients presenting with undifferentiated agitation. The purpose of this investigation was to compare the effectiveness and safety of these agents for acute agitation in the ED. METHODS: This was a retrospective observational study conducted at an urban, academic ED. The primary endpoint was time from the first dose of study medication to restraint removal. Safety endpoints included incidence of bradycardia (heart rate < 60 bpm), hypotension (systolic blood pressure < 90 mmHg), hypoxia (oxygen saturation < 90% or need for respiratory support), and incidence of intubation for ongoing agitation or respiratory failure. RESULTS: An initial 189 patients were screened, of which, 92 met inclusion criteria. The median time from initial drug administration to restraint removal was 49 min (IQR 30, 168) in the ketamine group and 43 min (IQR 30, 80) in the droperidol group (Median difference 6 min; 95% CI [-7, 26]). There was no significant difference in rates of bradycardia (3% vs 3%, 95% CI [-7%, 8%]), hypotension (0% vs 2%, 95% CI [-5%, 2%]), or hypoxia (7% vs 10%, 95% CI [-15%, 9%]) in the ketamine versus droperidol groups respectively. One patient in the ketamine group was intubated for ongoing agitation, and one patient in the droperidol group was intubated for respiratory failure. CONCLUSIONS: Intramuscular droperidol and intramuscular ketamine were associated with similar times from drug administration to restraint removal in patients presenting to the ED with undifferentiated agitation. Prospective studies are warranted to evaluate IM droperidol and IM ketamine head-to-head as first line agents for acute agitation in the ED.

Impact of intravenous calcium with diltiazem for atrial fibrillation/flutter in the emergency department.

OBJECTIVE: The purpose of this study was to evaluate the effect of early intravenous (IV) calcium on systolic blood pressure (SBP) when administered with IV diltiazem in subjects with atrial fibrillation (AF) or flutter (AFL) with rapid ventricular response (RVR) in the Emergency Department (ED). METHODS: This was a multicenter, retrospective cohort study that evaluated adults admitted to the ED with documented AF or AFL, heart rate (HR) > 120 bpm, SBP 90 to 140 mmHg, and received treatment with IV diltiazem for rate control. The primary outcome was the change in SBP 60 min (+/- 30 min) after initial IV diltiazem administration. Secondary outcomes included time to initial rate control (HR < 100 bpm), time to sustained rate control (HR < 100 bpm for 3 h), change in HR, rates of hypotension, bradycardia, hypercalcemia, and line extravasation within 24 h of initial diltiazem administration. RESULTS: There were 198 subjects in the diltiazem monotherapy group and 56 subjects in the diltiazem with calcium group meeting the inclusion criteria. The primary outcome, median change in SBP 60 min after initial IV diltiazem administration, was similar between groups (-2 mmHg vs -1.5 mmHg; p = 0.642), but this difference was not statistically significant. All secondary outcomes were found to be similar between groups. Although not statistically significant, hypotension occurred more often in the diltiazem with calcium group (20.2% vs 32.1%; p = 0.060) while bradycardia occurred more often in the diltiazem monotherapy group (4.5% vs 0%; p = 0.213). In terms of achieving rate control, the administration of calcium with diltiazem did not significantly change the time to initial rate control (1.4 h vs 1.8 h; p = 0.141) or time to sustained rate control (7.9 h vs 7.7 h; p = 0.570) compared to diltiazem alone. CONCLUSIONS: In the setting of AF/AFL with RVR, administration of IV calcium with IV diltiazem did not show a significant impact on clinical or safety outcomes compared to IV diltiazem monotherapy.

IF IM in a crisis: Intranasal fentanyl versus intravenous morphine in adult vaso-occlusive crisis.

IMPORTANCE: Studies have demonstrated the benefits of INF in reducing pain scores in pediatric patients with VOC due to sickle cell disease (SCD) and in adult patients with chronic pain conditions other than VOC, such as cancer. However, there is limited literature that exists describing the role of INF in adult patients with VOC due to SCD. Current literature demonstrates that the use of IV morphine for VOC patients leads to reduced pain. Therefore, comparing the use of INF with IV morphine will establish the degree of effectiveness of INF for VOC patients. OBJECTIVE: To determine if intranasal fentanyl is equally as effective as IV morphine for treating VOC-associated pain in adult SCD patients. DESIGN: This study was a retrospective non-inferiority cohort study. Electronic health records were utilized to identify eligible patients between January 1, 2021 to February 28, 2022. Patients who received INF as an initial opioid upon presentation to the ED where allocated to the intervention group. On the other hand, individuals who received IV morphine as an initial opioid upon presentation to the ED were allocated to the control group. SETTING: A multi-site healthcare system containing five hospitals. PARTICIPANTS: Patients 18 years of age or older, admitted to the ED with VOC due to SCD, and received INF or IV morphine as an initial opioid upon presentation to the ED. MAIN OUTCOMES AND MEASURES: The primary outcome was to evaluate the percent change in pain reduction after the initial dose of opiate between groups. Secondary outcomes include time to first rescue medication, total morphine milligram equivalent (MME) of IV opiates, hypotension, bradycardia, respiratory distress requiring opiate reversal within 6 h post- study drug administration, readmission within 48 h, and ED disposition. RESULTS: A total of 230 patients were reviewed within the study period, 95 subjects met inclusion criteria, 31 subjects were included in the INF arm and 64 subjects in the IV morphine arm. The primary outcome showed an average percent pain reduction of 17.25% in the INF arm and 17.15% in the IV morphine arm. The point estimate difference was 0.1% (95% CI -9.3%-9.5%; non-inferiority (p < 0.0001). The median dose of IV opiates was 8 MME in the INF group, and 6 MME in the IV morphine group (p = 0.0268). The time from study drug to first rescue medication administration was 22.4 min and 27.3 min in the INF and IV morphine groups, respectively (p = 0.2231). There was no incidence of hypotension or respiratory distress requiring opiate reversal in either arm. Bradycardia occurred in 12.9% and 7.7% (p = 0.2042), readmission rates within 48 h due to VOC was 6.5% and 20.9% (p = 0.0553), and discharge from the ED to home was 16% and 66% (p = 0.0196) in INF and IV morphine arms, respectively. CONCLUSION: INF provided similar pain reduction compared to IV morphine in the treatment of adults with VOC presenting to the ED. IV morphine arm showed a statistically significant difference in discharge to home from the ED, however there was a trend in readmission within 48 h. The study showed no significant difference in hypotension, respiratory distress, or bradycardia between the groups. The INF group had no significant impact on time to drug administration compared to IV morphine, however it was within 1 h of patient presentation which complies with American Society of Hematology (ASH) guidelines. In conclusion, our study showed that INF was non-inferior when compared to IV morphine in reducing pain scores after drug administration. Therefore, INF is an effective alternative to IV morphine for pain management in adults presenting to the ED for VOC particularly in those with limited IV access.

Effect of GR205171 on autonomic dysreflexia induced by colorectal distension in spinal cord injured rats.

STUDY DESIGN: Preclinical pharmacology. OBJECTIVES: To determine whether blocking substance P signaling attenuates the hypertension and bradycardia evoked by colorectal distension (CRD) in spinal cord injured (SCI) rats. SETTING: University laboratory in Pennsylvania, U.S.A. METHODS: Tachykinin NK1 receptor antagonists were administered 30 min prior to CRD three weeks after complete spinal cord transection at the 4th thoracic (T4) level. The dose range, route of administration, and pretreatment time was based on published data demonstrating occupancy of brain NK1 receptors in rodents. RESULTS: Subcutaneous (SC) administration of 10-30 mg/kg GR205171 ((2S,3S)-N-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine dihydrochloride) reduced CRD-induced hypertension and bradycardia by 55 and 49%, respectively, compared with pretreatment values. There was no effect of GR205171 on resting blood pressure or heart rate. In contrast, the same dose range of CP-99,994 ((2S,3S)-N-[(2-methoxyphenyl)methyl]-2-phenyl-3-piperidinamine dihydrochloride) had no effect on CRD-induced cardiovascular responses. CONCLUSIONS: The effective dose range of GR205171 to alleviate autonomic dysreflexia is consistent with the blockade of NK1 receptors on pelvic sensory afferents in the lumbosacral spinal cord, which may in turn prevent the over-excitation of sympathetic preganglionic neurons (SPNs) that regulate blood pressure and heart rate. The findings provide preclinical support for the utility of NK1 receptor antagonists to treat autonomic dysreflexia in people with SCI. The difference in the effects of the two NK1 receptor antagonists may reflect the ~200-fold lower affinity of CP-99,994 than GR205171 for the rat NK1 receptor.

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

Severe bradycardia from severe hyperkalemia: Patient characteristics, outcomes and factors associated with hemodynamic support.

OBJECTIVE: Bradycardia is an under-studied manifestation of hyperkalemia potentially associated with adverse outcomes. We sought to systematically describe emergency department (ED) patients that present with severe bradycardia (heart rate < 50) associated with severe hyperkalemia (potassium ≥6.0 mEQ/L) and identify factors associated with the receipt of hemodynamic support. METHODS: Retrospective, single-center, case series performed at an urban, tertiary-care hospital from 1/1/2014 to 6/30/2020. We included consecutive adult ED patients presenting simultaneously with severe bradycardia and severe hyperkalemia. Patients with prehospital cardiac arrest, hemolyzed potassium specimens, or only point-of-care lab results were excluded. Detailed information, including chronic medications, electrocardiogram (ECG) features, and potassium/heart rate-directed treatments, was abstracted from the ED medical record. Intensive care utilization and in-hospital outcomes were also recorded. Factors associated with receipt of bradycardia-targeted treatment in the ED were determined with univariate comparisons. RESULTS: We screened 319 records and included 87 patients [mean age 72.5 (95% CI 53-92), 55% female, median heart rate 43 (38-47) beats/min, mean potassium 7.1 (95% CI 5.6-8.7) mEQ/L]. Cardiovascular (hypertension 82%, congestive heart failure 28%) and renal (dialysis dependence 30%) comorbidities were common. Many patients were prescribed negative chronotropic agents (84%) or potassium-retaining (52%) chronic medications. Common presenting scenarios were missed hemodialysis, isolated acute renal failure, or acute renal failure in the setting of concomitant critical illness. ECG revealed: junctional rhythm (39%), peaked T waves (27%), and QRS prolongation (30%). Twenty-eight (32%) patients exhibited hypotension and 34 (40%) altered mentation. Thirty-three (38%) patients received hemodynamic support, including 12 (14%) requiring temporary cardiac pacing. Forty-two (48%) patients received emergent renal replacement therapy and 57 (66%) were admitted to the intensive care unit. Hospital mortality was 10%. Factors associated with receipt of hemodynamic-targeted treatment included a lack of dialysis dependence, junctional rhythm, and concomitant presentation with hypothermia, acidemia, or sepsis. CONCLUSIONS: Patients presenting with severe bradycardia represent a unique phenotype of ED patients with hyperkalemia that may require significant resuscitation and critical care resources. Further research on the treatment of this uncommon, but potentially life-threatening condition is needed.

Systemic toxicity from subcutaneous brimonidine injection successfully treated with naloxone.

Brimonidine is a topical ophthalmic alpha-2 adrenergic agonist solution used to treat glaucoma. The toxidrome includes drowsiness, lethargy, hypotension, bradycardia, and respiratory depression when ingested in infants. We report a case of intentional subcutaneous injection of brimonidine in an elderly patient resulting in hypotension and CNS depression that responded to naloxone. A 73-year-old female with a past medical history significant for glaucoma, hypertension, and indwelling pacemaker presented to the emergency department after injecting her brimonidine tartrate ophthalmic solution subcutaneously (SQ). The patient was not taking any antihypertensive medications or opioids. Initial presentation consisted of lethargy, a paced rhythm of 60 bpm, and blood pressure of 91/24 mmHg with a MAP of 46. Due to central nervous system depression, 3 mg of intranasal naloxone was administered. The patient was treated with intravenous fluids and escalating doses of naloxone and required a continuous infusion. Mental status and vital signs subsequently improved. The patient was admitted to the ICU and naloxone was subsequently weaned over 12 h. Systemic central alpha-2 adrenergic agonist toxicity resulted from SQ brimonidine injection. Central alpha-2 adrenergic agonist overdoses present as sympatholytic effects including CNS depression, bradycardia, hypotension, and may mimic the opioid toxidrome. Brimonidine SQ injection has not previously been reported and this case has similar findings to other central alpha-2 adrenergic agonist poisonings. Naloxone has previously shown variable reversal of CNS depression in central alpha-2 overdose. In this case, high-dose naloxone was useful for reversing CNS depression and hemodynamic instability.

Three new categories of hypoglycaemic agents and various cardiovascular diseases: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: New hypoglycaemic agents consist of dipeptidyl peptidase four inhibitors (DPP4is), glucagon-like peptide one receptor agonists (GLP1RAs) and sodium-glucose cotransporter two inhibitors (SGLT2is). We aimed to define the association between each category of these new hypoglycaemic drugs and various cardiovascular diseases. METHODS: Large randomized trials comparing DPP4is, GLP1RAs or SGLT2is with placebo were included. Outcomes of interest were 95 kinds of cardiovascular diseases. Meta-analysis was conducted to generate pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS AND DISCUSSION: Twenty-one large randomized trials were included in this meta-analysis. Compared with placebo, SGLT2is were associated with the lower risks of hypertension (RR 0.67, 95% CI 0.49-0.93), atrial fibrillation (RR 0.78, 95% CI 0.67-0.91), bradycardia (RR 0.60, 95% CI 0.40-0.89) and heart failure (RR 0.74, 95% CI 0.68-0.80); GLP1RAs were associated with the lower risk of peripheral arterial occlusive disease (RR 0.73, 95% CI 0.56-0.97) and with the higher risk of deep vein thrombosis (RR 2.12, 95% CI 1.32-3.4), while DPP4is were associated with the lower risk of peripheral ischaemia (RR 0.57, 95% CI 0.37-0.89). WHAT IS NEW AND CONCLUSIONS: Our meta-analysis revealed that SGLT2is were associated with the lower risks of hypertension, atrial fibrillation, bradycardia and heart failure; GLP1RAs were associated with the lower risk of peripheral arterial occlusive disease and with the higher risk of deep vein thrombosis, while DPP4is were associated with the lower risk of peripheral ischaemia. These findings propose that each category of these new hypoglycaemic agents should be avoided or preferred in patients at high risks of specific cardiovascular diseases.

Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats.

Comorbid diabetes and depression constitutes a major health problem, worsening associated cardiovascular diseases. Fluoxetine's (antidepressant) role on cardiac diabetic complications remains unknown. We determined whether fluoxetine modifies cardiac vagal input and its serotonergic modulation in male Wistar diabetic rats. Diabetes was induced by alloxan and maintained for 28 days. Fluoxetine was administered the last 14 days (10 mg/kg/day; p.o). Bradycardia was obtained by vagal stimulation (3, 6 and 9 Hz) or i.v. acetylcholine administrations (1, 5 and 10 µg/kg). Fluoxetine treatment diminished vagally-induced bradycardia. Administration of 5-HT originated a dual action on the bradycardia, augmenting it at low doses and diminishing it at high doses, reproduced by 5-CT (5-HT1/7 agonist). 5-CT did not alter the bradycardia induced by exogenous acetylcholine. Decrease of the vagally-induced bradycardia evoked by high doses of 5-HT and 5-CT was reproduced by L-694,247 (5-HT1D agonist) and blocked by prior administration of LY310762 (5-HT1D antagonist). Enhancement of the electrical-induced bradycardia by 5-CT (10 µg/kg) was abolished by pretreatment with SB269970 (5-HT7 receptor antagonist). Thus, oral fluoxetine treatment originates a decrease in cardiac cholinergic activity and changes 5-HT modulation of bradycardic responses in diabetes: prejunctional 5-HT7 receptors augment cholinergic-evoked bradycardic responses, whereas prejunctional 5-HT1D receptors inhibit vagally-induced bradycardia.

[Effect of dexamethasone combined with oxybuprocaine hydrochloride gel on prevention of postoperative sore throat after nasal endoscopy].

OBJECTIVE: To explore the effectiveness and feasibility of dexamethasone combined with oxybuprocaine hydrochloride gel on the prevention of postoperative sore throat after nasal endoscopy. METHODS: In the study, 60 patients with American Society of Anesthesiologist (ASA) physical statuses Ⅰ to Ⅱ, aged 18 to 72 years, scheduled for elective nasal endoscope surgery under general anesthesia requiring endotracheal intubation were randomly divided into dexamethasone combined with oxybuprocaine hydrochloride gel group (G group, n=30) and control group (C group, n=30). The patients in the G group received dexamethasone 0.1 mg/kg before induction and the oxybuprocaine gel was applied to the endotracheal catheter cuff and the front end within 15 cm. The patients in the C group received the same dose of saline and the saline was applied to the endotracheal catheter cuff and the front end within 15 cm. Then, all the patients in the two groups received the same induction and anesthesia maintainance. The operation time, anesthesia time, emergence time, extubation time and departure time were recorded. The intraoperative infusion volume, blood loss volume, propofol, remifentanil, rocuronium dosage were also recorded. The adverse reactions such as intraoperative hypotension, bradycardia and postoperative agitation were recorded. The postoperative sore throat score was recorded at the end of operation and 4 h, 8 h, 12 h, and 24 h after operation. RESULTS: Compared with the C group, the emergence time [(8.4±3.9) min vs. (10.8±4.7) min], extubation time [(8.8±3.7) min vs. (11.9±4.8) min], and departure time [(20.0±5.3) min vs. (23.0±5.8) min] were significantly shorter, and the propofol dosage [(11.8±1.8) mg/kg vs. (15.9±4.6) mg/kg], remifentanil dosage [(10.9±4.7) µg/kg vs. (14.1±3.6) µg/kg] were significantly less in the G group, and there was no difference of rocuronium dosage in the two groups. Compared with the C group the incidence of intraoperative hypotension [10%(3/30) vs. 30%(9/30)], bradycardia [16.7%(5/30) vs. 20%(6/30)] and postoperative agitation [6.7%(2/30) vs. 23.3%(7/30)] were significantly lower in the C group. The postoperative sore throat score at the end of operation, 4 h, 8 h, 12 h and 24 h after operation in the G group were significantly lower than in the C group respectively [0 (0, 1) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (1, 2), 0 (0, 0) vs. 1 (0.75, 1), 0 (0, 0) vs. 1 (0, 1)]. CONCLUSION: Dexamethasone combined with oxybuprocaine hydrochloride gel was effective and feasible on the prevention of postoperative sore throat after nasal endoscopy.

Cardiovascular responses to putative chemoreceptor stimulation of embryonic common snapping turtles (Chelydra serpentina) chronically incubated in hypoxia (10% O2).

Developmental hypoxia has been shown to result in significant changes in cardiovascular development of American alligators and common snapping turtles. These include similar effects on cardiac mass and aspects of cardiovascular function. However, given the distant phylogenetic relationship between crocodilians and chelonians, we hypothesized that snapping turtles would also exhibit differences in the effects of developmental hypoxia on cardiovascular regulation. This hypothesis was based in part on prior studies that documented differences in plasticity of vagal tone on the heart between alligators and snapping turtles incubated in hypoxic conditions. To test this hypothesis, we investigated how 10% O2 exposure over final 80% of incubation altered the heart rate and blood pressure response to two chemical manipulations of the "chemoreflex" in common snapping turtles at 70% and 90% of incubation. NaCN injections produced a dose dependent bradycardia that was mediated by cholinergic receptor stimulation. This reflex was relatively unaffected by hypoxic incubation conditions in snapping turtle embryos. Injections of the 5-HT3 agonist phenylbiguanide (PBG) caused a pronounced bradycardia that decreased in intensity at 90% of incubation in embryos from the normoxic group while the heart rate response was unchanged in the hypoxic group. This differs from the previously reported diminished heart rate response of embryonic alligators incubated in 10% O2, suggesting plasticity in this chemoreflex response differs between the species. Our data also indicate the cardiovascular response is mediated by a secondary cholinergic receptor stimulation however the inability of ganglionic blockade to inhibit the PBG response leaves the location of the receptors antagonized by PBG in question in embryonic snapping turtles. Primarily, our findings refute the hypothesis that hypoxic incubation decreases the "chemoreflex' response of snapping turtle embryos.

Glucose Levels during the First 24 Hours following Perinatal Hypoxia.

OBJECTIVE: Hypoglycemia is a significant risk factor for perinatal brain injury and adverse outcomes, particularly in infants requiring resuscitation following hypoxic ischemic (HI) insult. We aimed to study blood glucose (BG) levels in physiologically stressed infants in the presence or absence of epinephrine (Epi) administration at resuscitation in the first 24 hours after birth. STUDY DESIGN: A retrospective chart review of all infants with heart rate (HR) < 100/min at 1 minute requiring positive pressure ventilation (PPV) at birth was performed. Infants were classified into two groups as follows: (1) PPV group: infants' HR improved with PPV only at resuscitation, and Epi group: infants received Epi at resuscitation for persistent bradycardia. Serial measurements of BG levels collected and glucose infusion rate (GIR) calculated at 24 hours. RESULTS: By design, infants in the Epi group had lower cord pH and higher base deficit. BG was significantly lower overtime in premature infants ≤32 weeks of gestation in the Epi group. The BG was markedly higher in near-term and term infants in the Epi group compared with the PPV group. Hypoglycemia was more common despite administration of higher GIR in premature infants ≤32 weeks of gestation. CONCLUSION: In the presence of physiological stress, premature infants are more at risk for hypoglycemia than term infants.

Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 Pneumonia Who Developed Bradycardia.

OBJECTIVE: To assess the clinical characteristics and clinical outcomes of bradycardic patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: The electronic medical records of 221 consecutive patients hospitalized for COVID-19 pneumonia between June and September 2020 were retrospectively reviewed. Patient characteristics, electrocardiographic data, and clinical and laboratory information were retrospectively collected. Patients not treated with drugs that blunt chronotropic response (nodal) were analyzed separately. RESULTS: Only patients whose heart rate was <60 beats per minute (bpm) (136/221, 61.5%) were included. Serial electrocardiography revealed that most patients (130/137, 97.7%) remained in sinus rhythm. The heart rate was between 50 and 59 bpm in 75% of the patients, while 18.4% were in the 40 to 49 bpm range, and 6.6% were <40 bpm. Medians for development of bradycardia after swab polymerase chain reaction positivity and duration of bradycardia were 41 hours and 5 days, respectively. Bradycardia resolved in 81 patients (59.6%). There were no statistically significant differences in outcomes according to degree of bradycardia (<50 vs 50-59, all P ≥ 0.073). No significant differences were noted for the overall cohort when comparing COVID-19 treatments according to resolution of bradycardia; however, when considering only the patients who were not receiving a nodal agent or antiarrhythmic, treatment with lenzilumab was more common in patients with resolution of bradycardia than patients without resolution of bradycardia (12.2% vs 0.0%, P = 0.030). CONCLUSIONS: Sinus bradycardia occurs frequently in patients with severe COVID-19, but the degree of bradycardia does not correlate with clinical outcomes. Lenzilumab may be associated with the resolution of bradycardia.

The antidotes atropine and pralidoxime distinctively recover cardiorespiratory components impaired by acute poisoning with chlorpyrifos in rats.

In a previous work we showed that the organophosphate pesticide (OP) chlorpyrifos (CPF) reduces the protective chemoreflex and baroreflex responses in rats. However, whether the antidotes atropine (ATR) and pralidoxime (2-PAM) are capable of restoring these reflex functions remains unexplored. Rats were poisoned with CPF (30 mg.kg-1, i.p.) and one hour after the intoxication, ATR (10 mg.kg-1, i.p.) and 2-PAM (40 mg.kg-1, i.p.) were administrated separately or in combination. Cardiorespiratory parameters were recorded in awake rats 24 h after CPF. Systolic blood pressure (SBP) and heart rate (HR) variability and spontaneous baroreflex sensitivity (sBRS) were derived from undisturbed recordings (30 min), while chemoreflex was assessed through potassium cyanide (KCN) i.v. injections (10, 20, 40, 80 µg/rat). CPF poisoning increased SBP variability and low frequency/high frequency (LF/HF) ratio of the HR variability spectrum, indicating autonomic imbalance with increased cardiac sympathetic tone. sBRS was not changed. Treatment with 2-PAM restored SBP variability, whilst both antidotes increased LF/HF ratio. CPF poisoning reduced the hypertensive, bradycardic and tachypneic chemoreflex responses. Chemoreflex-induced hypertensive response was restored by 2-PAM treatment, while ATR recovered the bradycardic response. Both antidotes restored the chemoreflex tachypneic response. Our data show distinct effects of ATR and 2-PAM on cardiorespiratory parameters affected by OP poisoning. While 2-PAM rescued the chemoreflex hypertensive response, ATR reversed chemoreflex bradycardic dysfunction. Although 2-PAM clinical use is questioned in some countries, our data indicate that summation of effects of both antidotes appears beneficial on the cardiorespiratory system and peripheral chemoreflex function.

The efficacy of intramuscular ephedrine in preventing hemodynamic perturbations in patients with spinal anesthesia and dexmedetomidine sedation.

Dexmedetomidine is used for sedation during spinal anesthesia. The sympatholytic effect of dexmedetomidine may exacerbate hypotension and bradycardia with spinal anesthesia. This study investigated the effects of prophylactic intramuscular injection of ephedrine in preventing hypotension and bradycardia occurring through combined use of spinal anesthesia and dexmedetomidine. One hundred sixteen patients scheduled for lower extremity orthopedic surgery were randomized into two groups receiving either ephedrine 20 mg intramuscularly or equivalent amount of 0.9% NaCl, both with dexmedetomidine and spinal anesthesia. The primary endpoint was the incidence of hemodynamic perturbations (hypotension or bradycardia event). The secondary endpoint was a rescue doses of ephedrine and atropine. The incidence of hemodynamic perturbations was significantly lower in the ephedrine group compared with to the saline group (26.3% versus 55.9%, p = 0.001). The rescue doses of atropine (0.09 ± 0.21 versus 0.28 ± 0.41, p = 0.001) and ephedrine (1.04 ± 2.89 versus 2.03 ± 3.25, p = 0.007) were also significantly lower in the ephedrine group. There was no differences in number of patients with hypertensive (7.0% versus 11.9%, p = 0.375) or tachycardia (1.8% versus 3.4% p = 0.581) episodes. The use of ephedrine intramuscular injections may be a safe and efficacious option in preventing hemodynamic perturbations in patients who received spinal anesthesia and sedation using dexmedetomidine.

Spontaneous brain arteriovenous malformation rupture with atrioventricular block in a pediatric patient.

This case reports 9 year-old-female with atrioventricular block and seizure. Careful evaluation, including electrocardiogram (ECG) and computerized tomography (CT) revealed a high-grade atrioventricular block and spontaneous brain arteriovenous malformation (AVM) rupture. The patient had complete resolution of her bradycardia and AV block following atropine. This case is to our knowledge the first description of a pediatric spontaneous brain AVM rupture presenting with high degree AV block responsive to intravenous atropine.

"Preventive" pacing in patients with tachy-brady syndrome (TBS): Confirming a common practice.

AIMS: Many tachy-brady syndrome (TBS) patients, are implanted a permanent pacemaker (PPM) to allow continuation of anti-arrhythmic drug (AAD) therapy to maintain sinus rhythm. Many of these PPM's are implanted as a preventive measure, in absence of symptomatic bradycardia. Our primary aim was to evaluate pacing use among these patients and find predictors for PPM use. Our secondary aim was to appreciate the portion of these patients who progress to permanent atrial fibrillation (AF). METHODS: Retrospective study of TBS patients implanted a PPM as preventive measure, dividing cases into defined categories regarding highest percent atrial and ventricular pacing documented in PPM clinic visits during 3 year follow-up (F/U) period. Patients' baseline characteristics and AAD therapy were compared between cases with a major (>90%) pacing use and cases with <90% pacing use to find predictors for pacing use. Multivariable logistic regression was applied to identify independent variables associated with major pacing use. RESULTS: Our study included 119 TBS patients. Most (86.5%) TBS patients had a moderate (>50%) pacing use and 58% had a major pacing use. Significant association was found between pre-implant severe sinus bradycardia (<40 bpm), first degree atrioventricular block and amiodarone treatment to major pacing use on univariate analysis and severe sinus bradycardia was significantly associated with major pacing on multivariate analysis as well. Only minority (16.8%) of TBS patients progressed to permanent AF during the study F/U period. CONCLUSION: Our study reveals most TBS patients succeed to maintain sinus rhythm using an AAD with a significant pacing use, suggesting preventive PPM implantation might be advantageous in these cases. Pre-implant severe sinus bradycardia (<40 bpm) is a possible predictor for major pacing use in this population.