Pain Sensation during Intradermal Injections of Three Different Botulinum Toxin Preparations in Different Doses and Dilutions

BACKGROUND: Pain sensation associated with injections of botulinum neurotoxin (BoNT) is commonly reported. To date differences in pain sensation between the commercially available products containing BoNT have not been quantified. OBJECTIVES: The pain sensations during injection of Dysport, Botox, Neurobloc, and pure saline (control) were compared. In addition, the nociceptive effect of different volumes used for the dilution of the same BoNT dose was investigated. METHODS: In a prospective, double-blind, controlled trial, 10 healthy subjects were injected intradermally with Dysport (12 U), Botox (3 and 4 U), Neurobloc (150 and 300 U) reconstituted in 0.9% saline, and pure saline. Pain sensation was quantified during injections. RESULTS: Neurobloc injections caused significantly more injection pain than Botox, Dysport, and saline. No significant differences between Dysport, Botox, and saline were found, although there was a trend toward less pain with pure saline injections. Higher pain levels with higher volumes could not be demonstrated significantly. CONCLUSION: Our data demonstrate that BoNT type B injections are associated with substantial pain. There is a considerable difference between the commercially available BoNT type B compared to the two BoNT type A preparations. Therefore, considering mitigation of injection pain seems necessary when using BoNT type B.     

A Simple Method for Preoperative Assessment of the Best Fitting Electrode Length in Single Lead VDD Pacing

For single lead VDD pacing, electrodes with various distances between the lead tip and the floating atrial dipole (AV distance) are available. Using different AV distances allows positioning of the atrial dipole in the mid- to high right atrium, regardless of the size of the right heart. In this position, reliable atrial sensing and rejection of ventricular far-field potentials can be expected. A simple test for the preoperative assessment of the best fitting AV distance in the individual patient was tested. We studied 24 consecutive patients prior to implantation of AVDD pacemaker. With the patient in supine position, a test electrode with an AV distance of 13 cm was taped onto the thorax. Under fluoroscopic control, it was moved until its course and projection onto the heart was equal to that of a ventricular lead. If fluoroscopy then showed a projection of the atrial dipole onto the mid- to high right atrium, a lead with a similar AV distance of 13 or 13.5 cm was used for implantation. If the atrial dipole projected itself too high or too low, a shorter or longer lead had to be implanted. The maximum time for the test was 2 minutes, and the maximum fluoroscopy time was 15 seconds. According to the test, a lead with an AV distance of 13 or 13.5 cm was implanted in 18 of 24 patients, and a lead with an AV distance of 15.5 or 16 cm was implanted in 6 of 24 patients. The atrial dipole could easily be positioned in the mid- to high right atrium in all patients, demonstrating a correct preoperative assessment of the best fitting AV distance. Intraoperatively, a P wave amplitude of 3.5 ± 3.0 mV was measured. The described test allows a fast and reliable assessment of the best fitting electrode length in single lead VDD pacing.     

Reduction of Pacing Output Coupling Capacitance for Sensing the Evoked Response

SPERZEL, J., et al. : Reduction of Pacing Output Coupling Capacitance for Sensing the Evoked Response. Sensing of the intracardiac evoked response (ER) after a pacing stimulus has been used in implantable pacemakers for automatic verification of capture. Reliable detection of ER is hampered by large residual afterpotentials associated with pacing stimuli. This led to the development of various technological solutions, like the use of triphasic pacing pulses and low polarizing electrode systems. This study investigated the effect of reducing the coupling capacitance (CC) in the pacemaker output circuitry on the magnitude of afterpotential, and the ability to automate detection of ventricular evoked response. A CC of 2.2 μF and four different blanking and recharge time settings were clinically tested to evaluate its impact on sensing of the ventricular ER and pacing threshold. Using an automatic step‐down threshold algorithm, 54 consecutive patients, aged 70 ± 10 years with acutely (n = 27 ) or chronically (n = 27 ) implanted ventricular pacing leads were enrolled for measurement testing. Routine measurements, using a standard pacing system analyzer (PSA), were (mean ± SD ) impedance 569 ± 155 Ω, R wave amplitude baseline to peak 9.8 ± 3.7 mV and threshold 0.9 ± 0.7 V at 0.4‐ms pulse width. This new capture verification scheme, based on a CC of 2.2 μF and recharge/blanking timing setting of 10/12 ms, was successful in 52 patients which is equivalent to a success rate of 96%. In a subgroup of 26 patients implanted with bipolar ventricular leads (10 chronic, 16 acute), data were collected in unipolar (UP) and bipolar (BP) pace/sense configurations. Also, ER signals were recorded with two different band‐pass filters: a wider band (WB) of 6–250 Hz and a conventional narrow band (NB) of 20–100Hz. WB sensing from UP lead configuration yielded statistically significant larger signal to artifact ratios (SAR) than the other settings (P < 0.01). A dedicated unipolar ER sensing configuration using a small output capacitor and a wider band‐pass filter enables adequate automatic capture verification, without any restrictions on pacing lead models or pacing/sensing configurations.     

Sleep-Disordered Breathing in Recipients of Implantable Defibrillators

Study Objectives: To examine the prevalence and clinical significance of sleep-disordered breathing in patients with implantable cardioverter defibrillators (ICD).
Methods and Results: Overnight sleep studies were performed in 129 ICD recipients who had no history of sleep apnea. The mean left ventricular ejection fraction (LVEF) was 29 ± 11%. Mild, moderate, and severe sleep apnea was diagnosed in the presence of an apnea/hypopnea index (AHI) of 5–15/h, 15.1–30/h, and >30/h, respectively. No sleep apnea was present in 49 patients (38%), 57 (44%) had central sleep apnea (CSA), and 23 patients (18%) had obstructive sleep apnea (OSA). Mild, moderate, and severe sleep apnea were present in 25%, 31%, and 44% of patients with CSA, compared with 52%, 22%, and 26% of patients with OSA (P < 0.05). LVEF was similar in patients with versus without OSA or CSA. Patients with CSA were significantly older and had a higher prevalence of ischemic cardiomyopathy than patients without sleep apnea.
Conclusions: Previously undiagnosed CSA is common in ICD recipients. Severely disordered breathing during sleep was more prevalent among patients with CSA than patients with OSA. This prospective, observational study will examine the long-term clinical significance of sleep-disordered breathing in ICD recipients.     

GONADOTROPHIN SECRETION IN THE SECOND HALF OF THE MENSTRUAL CYCLE: A COMPARISON OF WOMEN WITH NORMAL CYCLES, LUTEAL PHASE DEFECTS AND DISTURBED FOLLICULAR DEVELOPMENT

In order to study the relationship between episodic gonadotrophin secretion and alterations of ovarian hormone secretion, we examined women with normal menstrual cycles (n = 26), luteal phase defects (n = 10) or disturbed follicular oestradiol secretion (n = 8) as established by daily (except weekends) determinations of oestradiol and progesterone. Pulsatile gonadotrophin secretion was studied during the luteal phase or the second half of the menstrual cycle sampling at 15 min intervals for 12 h. LH and FSH mean concentrations and LH pulse frequency were significantly (P less than 0.01) increased in the group with disturbed follicular development in the presence of decreased oestradiol (E2) and progesterone (P4) levels. In women with luteal phase defects mean LH and FSH concentrations and pulsatile LH secretion showed a nonsignificant trend to lower values in the presence of significantly decreased P4 concentrations during the luteal phase.     

An Increase in Sinus Rate Following Radiofrequency Energy Application in the Posteroseptal Space

An increase in sinus rate has been previously described in patients with AV node reentry (AVNRT) following successful A V node modification. This increase could either be a specific sign of elimination of slow pathway conduction or it could be a consequence of energy application in the posteroseptal area. Thus, we compared the changes in sinus cycle length following successful slow pathway ablation (defined as complete elimination of dual AV node physiology) in patients having AVNRT with those in patients undergoing successful ablation of a posteroseptal atriovetriricular accessory connection. Twenty five patients (16 women and 9 men, mean age 41 ± 4 years) with typical AVNRT (cycle length 378 ± 12 ms and 29 patients (16 women and 13 men, age 34 ± 5 years) with an accessory connection (17 manifest and 12 concealed) were studied. The electrophysiology study was performed during sedation with Fentanyl and Midazolam. The mean number of energy applications was 3 ± 1 for successful slow pathway ablation and 4 ± 1 for successful ablation of the accessory connection (p:NS). Following the successful energy application, the sinus cycle length decreased significantly 776 ms at baseline to 691 ms in patients with AVNRT. Following successful ablation of the posteroseptal AC, sinus cycle length decreased from 755 ms at baseline to 664 ms (p < 0.05 in both groups [difference between groups not significant]). The decrease in sinus cycle length did not correlate with the number ofRF energy applications required for successful ablation or the total energy delivered. In conclusion, ablation of the AV node slow pathway and a posteroseptal accessory connection results in similar increases in the sinus rate. Thus, the increase in sinus rate is probably due to energy application in the posteroseptal space, possibly due to concomitant destruction of vagal inputs, and it is not specific for elimination of slow pathway conduction.     

Ventilation and Heart Rate Response During Exercise in Normals: Relevance for Rate Variable Pacing

The observation of a close relationship of heart rate to oxygen uptake (HH-VO₂) and heart rate to minute ventilation (HR-VE)has been shown to be of particular value in rate variable pacing. However, the impact of anaerobic threshold (AT)for the HH-VO₂ and HH-VE slope has been studied Jess. Twenty-three male and 16 female subjects, mean age 52 ± 7 years, were selected in whom complete heart catherization and extensive noninvasive sludies excluded major cardiopulmonary disease. Semisupine bicycle exercise testing with analysis of respiratory gas exchange was performed using a ramping work rate protocol with work increments of 20 watts/min. At the respiratory AT, determined by the V slope method, oxygen uptake (VO₂-AT)was 15.2 ± 3.0 mL/kg in males versus 13.8 ± 2.3 mL/kg in females and heart rate (HR-AT)was 109 ± 18 beats/min versus 119 ± 20 beats/min, respectively. Heart rate was highly correlated (r ±0.9)to VO₂ and minute ventilation (VE). A linear regression for HR-VO₂, however, was found only in 16/39 and for HR-VE in 11/39 subjects. Assuming the AT as the breakpoint of two linear curves, it could be demonstrated that compared to low exercise HR appeared to increase at maximal exercise more in relation to VO₂ but less in relation to VE; in men the individual slopes for HR-VO₂ were 2.6 ± 0.7 below but 3.2 ± 1.0 above AT (P < 0.05) and the slopes for HH-VE were 1.6 ± 0.5 below but 1.0 ± 0,4 above AT (P < 0.05). Similarly, in women the individual slopes for HR-VO₂ were 3.7 ± 1.4 below but 4.3 ± 1.4 above AT (P < 0.05)and the slopes for HR-VE were 2.1 ± 0.9 below but 1.3 ± 0.4 above AT (P < 0.05). The differences between male and female subjects were significant. The nonlinear behavior of the HB-VO₂ and HR-VE relation from rest to maximal exercise should have a particular impact in respiratory controlied pacing systems.     

Sudden Death in Pacemaker Patients

Of 264 pacemaker patients who died within 27.6 ± 21 months following pacemaker implantation, 36 (13.6%) died suddenly. There was no difference between them and the remaining patients in terms of age, sex, indications for pacing, type of pacemaker used, and interval between pacemaker implantation and death. On autopsy, all but one patient were found to show severe three-vessel disease without evidence of acute myocardial infarction. The cause of death would thus be compatible with malignant ventricular tachycardia.