QTc Changes Research Articles

Correction to: Implications of Individual QT/RR Profiles-Part 2: Zero QTc/RR Correlations Do Not Prove QTc Correction Accuracy in Studies of QTc Changes.

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Impact of Quetiapine Therapy on QTc Prolongation in Critically Ill Patients

Quetiapine is an atypical antipsychotic commonly utilized for the management of delirium in critically ill patients. The impact of quetiapine on QTc in the critically ill population is largely unknown. The purpose of this study was to evaluate QTc prolongation following administration of quetiapine for the management of delirium in critically ill patients. This was a single-center prospective, observational cohort study. QTc measurements of patients who received at least one dose of quetiapine were compared with a control group receiving melatonin. The primary outcome was mean change in QTc from baseline to maximum serum drug concentration after the first dose of quetiapine. No significant change in QTc was observed from baseline to post-quetiapine administration, with a mean change in QTc of 2.7 ms (438.4 ± 43.2 ms vs 441.1 ± 36.4 ms; P = 0.50). When comparing mean change in QTc between the quetiapine group and melatonin group, the difference was not significant (2.7 ± 37.8 ms vs -0.18 ± 32.0 ms, P = 0.73). Conclusion and Relevance: This study represents one of the first prospective studies evaluating the impact of quetiapine on QTc. The results of this study demonstrate a nonsignificant statistical and clinical change in the QTc following quetiapine administration in critically ill patients utilizing telemetry measurements. Routine QTc monitoring with formal electrocardiogram(s) following quetiapine administration may not be warranted.

A Comparison of the Effect of Sevoflurane and Propofol on Ventricular Repolarisation after Preoperative Cefuroxime Infusion.

The aim of this study is to investigate the changes in QT, QTc, and Tp-e intervals and Tp-e/QT ratio on surface electrocardiogram (ECG) signals during anaesthesia induction using propofol or sevoflurane after preoperative cefuroxime infusion. Some 120 cases of gynaecological patients are randomly divided into propofol (P) and sevoflurane (S) groups (n=60). After cefuroxime (1.5 g) was infused in the two groups of patients, propofol target controlled infusion (TCI) was conducted in the P group for 5 min to realise a plasma concentration of 4 μg/ml while patients in the S group inhaled anaesthesia by infusing 1.3 MAC sevoflurane for 6 min. The 12-lead ECGs were separately collected before infusing cefuroxime (T1), after infusing cefuroxime (T2), and after infusing propofol or sevoflurane (T3) to measure QT and Tp-e intervals, calculate QTc and Tp-e/QT, and record MAP and HR. Finally, we demonstrated that QT, QTc, and Tp-e intervals and Tp-e/QT ratio had no change (P > 0.05) after cefuroxime infusion in the two groups of patients compared with that before infusing antibiotics. Moreover, after conducting preoperative cefuroxime infusion, using propofol and sevoflurane had no influence on Tp-e interval, but sevoflurane can significantly prolong QT and QTc intervals (P < 0.05).

Telemetered common marmosets is useful for the assessment of electrocardiogram parameters changes induced by multiple cardiac ion channel inhibitors.

The objective of this study is to assess the response of telemetered common marmosets to multiple cardiac ion channel inhibitors and to clarify the usefulness of this animal model in evaluating the effects of drug candidates on electrocardiogram (ECG). Six multiple cardiac ion channel inhibitors (sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine) were orally administered to telemetered common marmosets and changes in QTc, PR interval and QRS duration were evaluated. Drugs plasma levels were determined to compare the sensitivity in common marmosets to that in humans. QTc prolongation was observed in the marmosets dosed with sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine. PR prolongation was noted after flecainide and verapamil administration, and QRS widening occurred following treatment with flecainide and quinidine. Drugs plasma levels associated with ECG changes in marmosets were similar to those in humans, except for verapamil-induced QTc prolongation. Verapamil-induced change is suggested due to body temperature decrease. These results indicate that telemetered common marmoset is a useful animal for evaluation of the ECG effects of multiple cardiac ion channel inhibitors and the influence of body temperature change should be considered in the assessment.

Intraoperative Change in QTc in a Patient with a Prolonged QTc Interval

Intraoperative Change in QTc in a Patient with a Prolonged QTc Interval

Evaluation of QTc Interval Prolongation Among Patients With Cancer Using Enteral Methadone.

The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known. To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer. Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Participants were divided into 3 methadone daily dose groups: <30 (low dose), 30 to 59 (moderate dose), ≥60 (high dose) mg. The primary outcome was the incidence of QTc prolongation (>450 ms for females and >430 ms for males). Secondary outcomes included the magnitude of change in QTc after starting methadone, the incidence of clinically significant QTc prolongation (>500 ms) and the prevalence of torsades de pointes and syncope. Two hundred three patients met study inclusion criteria: 91 (45%) low dose, 52 (26%) moderate dose, and 60 (29%) high dose. Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively ( P = .039, low vs high dose). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. For patients without QTc prolongation prior to initiating methadone, 62% of moderate-dose patients and 67% of high-dose patients had QTc prolongation, while taking methadone. This study found a notably high incidence of QTc prolongation in patients with cancer using enteral methadone. Future studies should aim to determine the risk of adverse cardiac effects in the cancer population and determine appropriate monitoring of methadone for pain management.

Lithium treatment in bipolar adolescents: a follow-up naturalistic study.

BackgroundAlthough lithium is currently approved for the treatment of bipolar disorders in youth, long term data, are still scant. The aim of this study was to describe the safety and efficacy of lithium in referred bipolar adolescents, who were followed up at the 4th (T1) and 8th (T2) month of treatment.MethodsThe design was naturalistic and retrospective, based on a clinical database, including 30 patients (18 males, mean age 14.2±2.1 years).ResultsMean blood level of lithium was 0.69±0.20 mEq/L at T1 and 0.70±0.18 mEq/L at T2. Both Clinical Global Impression-Severity (CGI-S) and Children Global Assessment Scale (C-GAS) scores improved from baseline (CGI-S 5.7±0.5, C-GAS 35.1±3.7) to T1 (CGI-S 4.2±0.70, C-GAS 46.4±6.5; P<0.001), without significant differences from T1 to T2. Thyroid-stimulating hormone significantly increased from 2.16±1.8 mU/mL at baseline to 3.9±2.7 mU/mL at T2, remaining within the normal range, without changes in T3/T4 levels; two patients needed a thyroid hormone supplementation. Creatinine blood level did not change. No cardiac symptoms and electrocardiogram QTc changes occurred. White blood cell count significantly increased from 6.93±1.68 103/mmc at baseline to 7.94±1.94 103/mmc at T2, and serum calcium significantly increased from 9.68±0.3 mg/dL at baseline to 9.97±0.29 mg/dL at T2, both remaining within the normal range; all the other electrolyte levels were stable and normal during the follow-up. The treatment with lithium was well tolerated, probably due to the relatively low lithium blood levels. Gastrointestinal symptoms (16.7%), sedation (9.7%) and tremor (6.4%) were the most frequently reported side effects.ConclusionLithium was effective and safe in adolescent bipolar patients followed-up for eight months.

Implications of Individual QT/RR Profiles-Part 2: Zero QTc/RR Correlations Do Not Prove QTc Correction Accuracy in Studies of QTc Changes.

IntroductionIn studies of drug-induced corrected QT (QTc) changes, fixed universal heart rate (HR) corrections (e.g., the Fridericia correction) are potentially misleading when assessing the effects of drugs that change HR. When data-specific corrections are designed, tests of their validity are needed. The proposed tests include zero correlations between QTc and corresponding RR values in the complete study data (pooling on-treatment and off-treatment interval measurements).ObjectiveTo document that this approach is potentially highly misleading, a statistical modeling study was conducted based on the full profiles of QT/RR data of 523 healthy subjects—254 females, mean age 33.5 years.MethodsIn each of the subjects, 50 baseline QT/RR readings were selected to model baseline data. In repeated experiments, groups of ten and 50 subjects were randomly selected and drug-induced HR increases between 0 and 25 beats per minute combined with QTc changes between − 20 and + 20 ms were modeled. In each experiment, subject-specific as well as population-specific HR corrections were designed so that the QTc interval data were uncorrelated to the corresponding RR interval data.ResultsThe simulation experiments showed that when zero correlations of QTc data with RR data are combined with more than trivial HR increases, the HR corrections are substantially biased and underestimate or fully eliminate any drug-induced QTc interval changes. This result is in full agreement with theoretical considerations of HR correction principles.ConclusionsThe lack of correlation of QTc versus RR durations including on-treatment data does not prove any validity of HR corrections. Correlations of QTc versus RR in study data pooling on- and off-drug measurements should not be used to prove the appropriateness of HR corrections.Electronic supplementary materialThe online version of this article (10.1007/s40264-018-0735-2) contains supplementary material, which is available to authorized users.

Mexiletine Usage in a Chronic Pain Clinic: Indications, Tolerability, and Side Effects

Intravenous lidocaine has multiple applications in the management of acute and chronic pain. Mexiletine, an oral lidocaine analogue, has been used in a number of chronic pain conditions although its use is not well characterized. To report our experience using mexiletine in a chronic pain population, specifically looking at tolerability, side effects, and EKG changes. Retrospective, cohort study. Three chronic pain clinics within a hospital system in Detroit, MI. All patients who had a mexiletine prescription between August 2015 and August 2016 were queried via the electronic medical record. Each chart was examined for demographics, QTc changes on EKG, length of use, and reasons for stoppage. There were 74 total patients identified in the chronic pain management clinics as receiving at least 1 mexiletine prescription over the 1-year time period. Twice as many women as men received mexiletine prescriptions. Neuropathic pain was the most common primary diagnosis (64%) which included diabetic neuropathy, radiculopathy, and others. Fibromyalgia was the next most common primary diagnosis (28%). A QTc change on the EKG showed a mean decrease of 0.1 ms and median increase of 1.5 ms. At 6 months (180 days), approximately 30% of the patients remained on mexiletine therapy, and 28% remained on the therapy at 1 year (360 days). Median duration of use was 60 days and the mean was 288 days. Neurologic and gastrointestinal side effects were the most commons reason for stoppage. All side effects were mild and resolved with stoppage. After side effects, lack of response, or loss of efficacy, were the next most common reasons for stoppage. Pain relief and outcomes were not specifically examined due to confounding factors including interventional treatments and multiple treatment modalities. This was a retrospective, cohort study limited to our specific clinic population with a relatively high loss to follow-up rate. Mexiletine is rarely a first line option for chronic pain management and is often used when multiple other modalities have failed. By reporting our experience, we hope other clinicians may have more familiarity with the drug's use in a chronic pain practice. It appears reasonably tolerable, may not require frequent EKG monitoring, and can be an appropriate adjunct in the chronic pain population. More research is needed regarding efficacy and dose titration for mexiletine in chronic pain. Chronic pain, mexiletine, IV lidocaine, pain, neuropathic pain, neuropathy, fibromyalgia, QTc, tolerability.

Heart Rate-corrected QT Interval Duration in Rheumatoid Arthritis and Its Reduction with Treatment with the Interleukin 6 Inhibitor Tocilizumab.

Individuals with rheumatoid arthritis (RA) are at a heightened risk of sudden cardiac death, an outcome increased in those with prolongation of the corrected electrocardiographic QT interval (QTc). We compared QTc between patients with RA and demographically matched controls and studied the change in QTc after treatment with the interleukin 6 inhibitor tocilizumab (TCZ). Standard 12-lead electrocardiograms were obtained and QTc was measured in patients with RA at baseline and after 24 weeks of TCZ treatment, then compared with non-RA controls who were frequency-matched on age and sex. Indicators of the baseline QTc and predictors of change in QTc were studied using multivariable linear regression. A total of 94 RA and 42 non-RA controls were studied. The average baseline QTc was 10 ms longer in the RA group vs controls (422 vs 412 ms, respectively; p < 0.001) and decreased to an average of 406 ms with treatment (p < 0.001). Baseline QTc was significantly and independently higher among those with anticyclic citrullinated peptide antibodies seropositivity, higher swollen joint counts, and higher levels of C-reactive protein (CRP) and matrix metalloproteinase 3. Each log unit decrease in CRP with treatment was associated with an average reduction in QTc of 2.9 ms (p = 0.002) after adjusting for age and baseline QTc. Clinical response measures were not associated with the change in QTc. The marked normalization of QTc observed with TCZ treatment, and its close parallel with CRP reduction, support the premise that systemic inflammation contributes to cardiac repolarization abnormalities in RA that may be amenable to treatment.

An increase in corrected QT interval may indicate a good clinical response to amitriptyline in female patients with burning mouth syndrome

Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of underlying causes. BMS patients can pose a therapeutic challenge to clinicians. Amitriptyline has been a first-line treatment for BMS and is known to prolong corrected QT interval (QTc) in a dose dependent manner. However, little is known about the QTc lengthening effect of amitriptyline at analgesic dosages. The objective of this study was to evaluate changes in QTc in female BMS patients treated with amitriptyline. We conducted a single-center retrospective observational study and evaluated 40 female BMS patients. The QTc interval did not show statistically significant increase with amitriptyline (p=0.1502). However, the change in QTc of amitriptyline-responders was significantly longer than that of nonresponders (p=0.0142). The change in QTc may be a non-invasive maker of clinical responses to amitriptyline in female BMS patients.

Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy

BackgroundNEPA, an oral fixed combination of the NK1RA netupitant (300mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline–cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235mg plus PALO 0.25mg) has been developed. Patients and methodsThis randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1–4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms. ResultsA total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed. ConclusionsIntravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.

Strategic and Statistical Considerations on the QT Assessment of Volasertib

Volasertib is a selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase (Plk). A potential for prolonged QT intervals was indicated with volasertib in preclinical studies and preliminary clinical data. As a result, electrocardiograms (ECGs) have been collected in all volasertib clinical trials to monitor potential cardiac effects. This article describes strategic and statistical methods prospectively planned to perform an integrated analysis of ECG data from available trials to evaluate volasertib’s effect on cardiac repolarization, as reflected by changes in the duration of QT interval and other ECG-related endpoints. Methods to effectively cope with heterogeneity between trials (ie, differences in study designs) are discussed. These strategies may be useful for other investigational drugs for which QT risk assessment is required, but a thorough QT/QTc trial is not feasible, resulting in the need for an alternative approach. Volasertib therapy relevantly prolonged adjusted mean QTcF change from administration baseline following the first and subsequent infusions. The integrated analysis revealed that the volasertib effects on the mean QTc changes from baseline were transient and had resolved at 24 hours after start of the first infusion. There was no evidence for a long-term impact on the QTcF interval following multiple infusions with volasertib.

Pretransplant increases in left ventricular volume and mass are associated with QT prolongation during pediatric liver transplantation.

Structural alterations in the cirrhotic heart may contribute to electromechanical abnormalities, represented by QT prolongation. The aim of this study was to investigate the changes in QTc according to the operative stage during pediatric LT and to identify which baseline echocardiographic parameters were associated with intraoperative QTc prolongation. Data were evaluated from 39 children undergoing LT for chronic liver disease (median age 9months). In 19 patients (48.7%), baseline QTc was prolonged ≥440ms (462±19ms). Through the period of post-reperfusion, QTI, QTc, and JTI progressively increased, although values partially recovered toward the end of surgery. High LVMI (≥82.51g/m2 ) was associated with baseline QTc≥440ms (OR=1.034, P=.032). In the 5minutes post-reperfusion stage, marked QTc prolongation (defined as QTc≥500ms; n=24, 61.5%) was significantly associated with high EDVI (OR=1.060, P=.027) and SVI (OR=1.075, P=.026). In children with chronic liver disease, increased ventricular volumes and mass may increase the risk of QTc prolongation during LT, suggesting that repolarization abnormalities might be contributed by structural changes characteristic of cirrhotic cardiomyopathy.

Effect of down-regulation of IKs repolarization-reserve on ventricular arrhythmogenesis in a guinea pig model of cardiac hypertrophy

To observe the changes of rapidly activated delayed rectifier potassium channel (IKr) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKr and IKs blocker on the incidence of ventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH). Methods: Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group. LVH model was prepared. Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH. The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers. Results: Compared with cardiac cells in the control group, the interventricular septal thickness at end systole (IVSs), left ventricular posterior wall thickness at end systole (LVPWs), QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P<0.05); while IKs densities were significantly reduced [+60 mV: (0.36±0.03) pA/pF vs (0.58±0.05) pA/pF, P<0.01]. However, LVH exerted no significant effect on IKr densities. IKr blocker markedly prolonged the QTc interval (P<0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs. In contrast, IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals. IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals. Conclusion: The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation of IKs.

Importance of QT/RR hysteresis correction in studies of drug-induced QTc interval changes

QT/RR hysteresis and QT/RR adaptation are interlinked but separate physiological processes signifying how quickly and how much QT interval changes when heart rate changes, respectively. While QT interval duration is, as a rule, corrected for heart rate in terms of the QT/RR adaptation, the correction for QT/RR hysteresis is frequently omitted in studies of drug-induced QTc changes. This study used data from previously conducted thorough QT studies to investigate the extent of QTc errors caused by omitting the correction for QT/RR hysteresis, particularly in small clinical investigations. Statistical modeling approach was used to generate 11,000 simulated samples of 10-subject studies in which mixed effect PK/PD models were used to estimate drug-induced QTc changes at mean maximum plasma concentration of investigated compounds. Calculations of QTc intervals involving and omitting QT/RR hysteresis correction were compared. These comparisons showed that ignoring QT/RR hysteresis has two undesirable effects: (A) In the design of subject-specific heart rate corrections (needed in studies of drugs that change heart rate) omission of QT/RR hysteresis may lead to signals of QTc prolongation of more than 10 ms to be missed. (B) Irrespective of whether the investigated drug changes heart rate, omission of QT/RR hysteresis causes the widths of the confidence intervals of the PK/PD predicted QTc interval changes to be increased by 20–30% on average (exceeding 50% in some cases). This may lead to a failure of excluding meaningful QTc prolongation which would be excluded if using hysteresis correction. The study concludes that correction for QT/RR hysteresis should be incorporated into future studies of drug-induced QTc changes. Subject-specific heart rate corrections that omit hysteresis correction may lead to erroneously biased conclusions. Even when using universal (e.g. Fridericia) heart rate correction, hysteresis correction decreases the confidence intervals of QTc changes and thus helps avoiding false positive outcomes.

Thoracoscopic Sympathectomy for Long QT Syndrome. Literature Review and Case Study

Multiple case studies have suggested that video-assisted thoracoscopic sympathectomy (VATS) reduces the occurrence and frequency of symptoms in long QT syndrome (LQTS) [1,2,3]. To date there has not been a literature review to report on the short-term and long-term outcomes of this procedure. Our primary aims are to review the literature findings on the clinical outcomes of VATS sympathectomy for long QT and present a local centre case report on the outcomes of T2-T5 sympathectomy. Relevant articles were identified by a systematic search of PubMed, Cochrane and Scopus databases, from November 1985 to October 2015. A total of 520 patients from 21 publications were included for analysis and discussion in three main areas: presenting symptoms and indication for surgery, perioperative complications, and patient quality of life following surgery. Our case study reviews a 49-year-old female with recently diagnosed long QT syndrome and intolerance to beta blocker therapy successfully managed with T2-T5 thoracic sympathectomy. The most common presenting indication for operative management of long QT syndrome was syncope (208/520 patients) and tachyarrhythmia (207/520 patients). T1-T5 left sympathectomy was performed in 15/21 published reports (332/520 patients) with partial stellate removal or in its entirety. Follow-up of patients ranged from 1 month to 11 years. Four patients died in the postoperative period, from fatal arrhythmias. The most common postoperative findings were no symptoms (64/520 patients); tachyarrhythmia (55/520 patients), syncope (45/520 patients), and Horner's syndrome (13/520 patients with 27 patients reporting associated symptoms). Thirteen cases reported on the QTc changes post sympathectomy and 9/13 cases involving 220/520 patients showed marked QTc reduction following surgery. Mean preoperative QTc was 558ms and median 559ms. Mean postoperative QTc was 476ms and median 466ms. Our patient showed a marked reduction in QTc following surgery, with no evidence of arrhythmias and reduced beta blocker dependence. Surgical management of LQTS has historically involved a left cervicothoracic stellectomy removing stellate ganglia and typically part of the left thoracic sympathetic chain resulting in reduction in symptoms but increasing the risk of Horner's syndrome and intermittent temperature changes [4,5]. Surgical resection of the thoracic ganglia alone for management of LQTS is scarce in the literature. Short-term follow-up in our case study following a T2-T5 sympathectomy revealed reduction in symptoms, no requirement for beta blocker therapy and reduced QTc interval. Further follow-up using greater patient numbers will further support T2-T5 sympathectomy as an option for surgical management of LQTS.

Effect of Intravenous Ondansetron on the QT Interval of Patients' Electrocardiograms

Ondansetron improves the success of oral rehydration in children with gastroenteritis. In postoperative adults, ondansetron has been shown to prolong the corrected QT (QTc). The aim of the study was to evaluate the effect of ondansetron on the QT at peak effect and at 1-hour postpeak effect in pediatric patients. This was an observational study looking at patients aged 6 months to 18 years receiving intravenous ondansetron for nausea, vomiting, or the inability to take fluids in the emergency department. Patients had electrocardiogram performed at baseline, at ondansetron's peak effect, and 1 hour postpeak effect. A paired samples Student t test compared QTc change at peak effect to zero. Peak effect of intravenous ondansetron is 3 minutes. One hundred patients were included. Fifty-five percent of patients were female with a mean age of 8.3 years. The mean (range) baseline QTc was 435 (388 to 501) milliseconds. The mean (range) change in QTc at peak effect of ondansetron was 3 (-40 to 65) milliseconds (P = 0.072). The change in QTc 1-hour postpeak effect of ondansetron was 3 (-43 to 45) milliseconds (P = 0.082). No change at peak effect or 1-hour postpeak effect was clinically significant. Ondansetron does not affect the QTc of pediatric patients receiving the medication for nausea, vomiting, or inability to take fluids in the emergency department. No changes in the QTc are clinically significant. To date, there have been no studies evaluating the effect of ondansetron in this acutely ill population; therefore, a larger study should be completed to confirm these data.

Study of Electrocardiographic QT and QTc Changes in Apparently Healthy Obese Young Women

Study of Electrocardiographic QT and QTc Changes in Apparently Healthy Obese Young Women

Dynamic QT Interval Changes from Supine to Standing in Healthy Children

BackgroundQT-interval variations in response to exercise-induced increases in heart rate have been reported in children and adults in the diagnosis of long QT syndrome (LQTS). A quick standing challenge has been proposed as an alternative provocative test in adults, with no pediatric data yet available. MethodsA standing test was performed in 100 healthy children (mean age, 9.7 ± 3.1 years) after 10 minutes in a supine position with continuous electrocardiographic recording. QT intervals were measured at baseline, at maximal heart rate, at maximal QT, and at each minute of a 5-minute recovery while standing. Measurements were taken in leads II/V5 and were corrected for heart rate (QTc). ResultsOn standing, the heart rate increased by 29 ± 10 beats per minute (bpm). The QT interval was similar at baseline and on standing (394 ± 34 ms vs 394 ± 34 ms; P = 1.0). However, QTc increased from 426 ± 21 to 509 ± 41 ms (P < 0.001). The 95th percentile for QTc at baseline and maximal heart rate was 457 ms and 563 ms, respectively. At 1 minute of recovery, the QT interval was shorter (375 ± 31 ms) compared with baseline (394 ± 34 ms; P < 0.001) and standing (394 ± 34 ms; P < 0.001). QTc reached baseline values after 1 minute of recovery and remained stable thereafter (423 ± 23 ms at 1 minute; 426 ± 22 ms at 5 minutes; P = 1.0). ConclusionsThis first characterization of QTc changes on standing in children shows substantial alterations, which are greater than those seen in adults. Two-thirds of the children would have been misclassified as having LQTS by adult criteria, indicating the need to create child-specific standards.